https://en.longevitywiki.org/api.php?action=feedcontributions&feedformat=atom&user=AdssxLongevity Wiki - User contributions [en-GB]2026-04-26T03:31:26ZUser contributionsMediaWiki 1.41.0https://en.longevitywiki.org/index.php?title=Selegiline&diff=3392Selegiline2024-12-06T13:47:03Z<p>Adssx: /* Dosage */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25 mg/kg, 3 times per week, '''subcutaneously'''.<ref name=":0" /> In a 2016 study, Knoll found that a lower dose of 0.001 mg/kg three times a week did not prolong lifespan significantly while 0.1 mg/kg three times a week prolonged life by 12%.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0024320516306257 Longevity study with low doses of selegiline/(−)-deprenyl and (2''R'')-1-(1-benzofuran-2-yl)-''N''-propylpentane-2-amine (BPAP)], Knoll & Miklya, Life Sciences, Volume 167, 15 December 2016, pp 32-38</ref><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
In a 2016 study, authors identified deprenyl as one of the 11 compounds (with acarbose, d-glucosamine, dihydroergocristine methanesulfonate, ellagic acid, fenofibrate, glutathione, metformin, spermidine, tyrosol, and vinpocetine) that fulfill all their proposed nine criteria for the evaluation of geroprotectors (Primary criteria: increased lifespan, amelioration of human aging biomarkers, acceptable toxicity, minimal side effects at therapeutic dosage, improving health-related quality of life. Secondary criteria: evolutionary conservatism of target or mechanism of action, reproducibility of geroprotective effects on different model organisms, simultaneous influence on several aging-associated causes of death in mammals, increase in stress resistance).<ref>Moskalev A, Chernyagina E, Tsvetkov V, Fedintsev A, Shaposhnikov M, Krut'ko V, Zhavoronkov A, Kennedy BK. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016 Jun;15(3):407-15. doi: 10.1111/acel.12463. Epub 2016 Mar 11. PMID: 26970234; PMCID: PMC4854916.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Mechanism ===<br />
According to Knoll's theory, Deprenyl is a catecholaminergic activity enhancer (CAE) and a small daily dose of a CAE is a suitable anti-aging therapy to fight the age-related slow decay of the catecholaminergic system.<ref>Miklya, I. The significance of selegiline/(−)-deprenyl after 50 years in research and therapy (1965–2015). ''Mol Psychiatry'' 21, 1499–1503 (2016). <nowiki>https://doi.org/10.1038/mp.2016.127</nowiki></ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 5 to 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
In rats administered with rotenone to reproduces Parkinson’s disease, the beneficial effects of deprenyl were augmented when combined with N-acetylcysteine (NAC).<ref>Khashab, R.; Gutman-Sharabi, N.; Shabtai, Z.; Landau, R.; Halperin, R.; Fay-Karmon, T.; Leibowitz, A.; Sharabi, Y. Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson’s Disease. ''Int. J. Mol. Sci.'' 2023, ''24'', 12522. <nowiki>https://doi.org/10.3390/ijms241512522</nowiki></ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=3370Selegiline2024-08-29T12:16:20Z<p>Adssx: /* Rodents */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25 mg/kg, 3 times per week, '''subcutaneously'''.<ref name=":0" /> In a 2016 study, Knoll found that a lower dose of 0.001 mg/kg three times a week did not prolong lifespan significantly while 0.1 mg/kg three times a week prolonged life by 12%.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0024320516306257 Longevity study with low doses of selegiline/(−)-deprenyl and (2''R'')-1-(1-benzofuran-2-yl)-''N''-propylpentane-2-amine (BPAP)], Knoll & Miklya, Life Sciences, Volume 167, 15 December 2016, pp 32-38</ref><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
In a 2016 study, authors identified deprenyl as one of the 11 compounds (with acarbose, d-glucosamine, dihydroergocristine methanesulfonate, ellagic acid, fenofibrate, glutathione, metformin, spermidine, tyrosol, and vinpocetine) that fulfill all their proposed nine criteria for the evaluation of geroprotectors (Primary criteria: increased lifespan, amelioration of human aging biomarkers, acceptable toxicity, minimal side effects at therapeutic dosage, improving health-related quality of life. Secondary criteria: evolutionary conservatism of target or mechanism of action, reproducibility of geroprotective effects on different model organisms, simultaneous influence on several aging-associated causes of death in mammals, increase in stress resistance).<ref>Moskalev A, Chernyagina E, Tsvetkov V, Fedintsev A, Shaposhnikov M, Krut'ko V, Zhavoronkov A, Kennedy BK. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016 Jun;15(3):407-15. doi: 10.1111/acel.12463. Epub 2016 Mar 11. PMID: 26970234; PMCID: PMC4854916.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Mechanism ===<br />
According to Knoll's theory, Deprenyl is a catecholaminergic activity enhancer (CAE) and a small daily dose of a CAE is a suitable anti-aging therapy to fight the age-related slow decay of the catecholaminergic system.<ref>Miklya, I. The significance of selegiline/(−)-deprenyl after 50 years in research and therapy (1965–2015). ''Mol Psychiatry'' 21, 1499–1503 (2016). <nowiki>https://doi.org/10.1038/mp.2016.127</nowiki></ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
In rats administered with rotenone to reproduces Parkinson’s disease, the beneficial effects of deprenyl were augmented when combined with N-acetylcysteine (NAC).<ref>Khashab, R.; Gutman-Sharabi, N.; Shabtai, Z.; Landau, R.; Halperin, R.; Fay-Karmon, T.; Leibowitz, A.; Sharabi, Y. Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson’s Disease. ''Int. J. Mol. Sci.'' 2023, ''24'', 12522. <nowiki>https://doi.org/10.3390/ijms241512522</nowiki></ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2946Selegiline2023-09-15T19:50:44Z<p>Adssx: /* Combination */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /> In a 2016 study, Knoll found that a lower dose of 0.001 mg/kg three times a week did not prolong lifespan significantly while 0.1 mg/kg three times a week prolonged life by 12%.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0024320516306257 Longevity study with low doses of selegiline/(−)-deprenyl and (2''R'')-1-(1-benzofuran-2-yl)-''N''-propylpentane-2-amine (BPAP)], Knoll & Miklya, Life Sciences, Volume 167, 15 December 2016, pp 32-38</ref><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
In a 2016 study, authors identified deprenyl as one of the 11 compounds (with acarbose, d-glucosamine, dihydroergocristine methanesulfonate, ellagic acid, fenofibrate, glutathione, metformin, spermidine, tyrosol, and vinpocetine) that fulfill all their proposed nine criteria for the evaluation of geroprotectors (Primary criteria: increased lifespan, amelioration of human aging biomarkers, acceptable toxicity, minimal side effects at therapeutic dosage, improving health-related quality of life. Secondary criteria: evolutionary conservatism of target or mechanism of action, reproducibility of geroprotective effects on different model organisms, simultaneous influence on several aging-associated causes of death in mammals, increase in stress resistance).<ref>Moskalev A, Chernyagina E, Tsvetkov V, Fedintsev A, Shaposhnikov M, Krut'ko V, Zhavoronkov A, Kennedy BK. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016 Jun;15(3):407-15. doi: 10.1111/acel.12463. Epub 2016 Mar 11. PMID: 26970234; PMCID: PMC4854916.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Mechanism ===<br />
According to Knoll's theory, Deprenyl is a catecholaminergic activity enhancer (CAE) and a small daily dose of a CAE is a suitable anti-aging therapy to fight the age-related slow decay of the catecholaminergic system.<ref>Miklya, I. The significance of selegiline/(−)-deprenyl after 50 years in research and therapy (1965–2015). ''Mol Psychiatry'' 21, 1499–1503 (2016). <nowiki>https://doi.org/10.1038/mp.2016.127</nowiki></ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
In rats administered with rotenone to reproduces Parkinson’s disease, the beneficial effects of deprenyl were augmented when combined with N-acetylcysteine (NAC).<ref>Khashab, R.; Gutman-Sharabi, N.; Shabtai, Z.; Landau, R.; Halperin, R.; Fay-Karmon, T.; Leibowitz, A.; Sharabi, Y. Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson’s Disease. ''Int. J. Mol. Sci.'' 2023, ''24'', 12522. <nowiki>https://doi.org/10.3390/ijms241512522</nowiki></ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2944Selegiline2023-09-14T10:58:44Z<p>Adssx: /* Rodents */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /> In a 2016 study, Knoll found that a lower dose of 0.001 mg/kg three times a week did not prolong lifespan significantly while 0.1 mg/kg three times a week prolonged life by 12%.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0024320516306257 Longevity study with low doses of selegiline/(−)-deprenyl and (2''R'')-1-(1-benzofuran-2-yl)-''N''-propylpentane-2-amine (BPAP)], Knoll & Miklya, Life Sciences, Volume 167, 15 December 2016, pp 32-38</ref><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
In a 2016 study, authors identified deprenyl as one of the 11 compounds (with acarbose, d-glucosamine, dihydroergocristine methanesulfonate, ellagic acid, fenofibrate, glutathione, metformin, spermidine, tyrosol, and vinpocetine) that fulfill all their proposed nine criteria for the evaluation of geroprotectors (Primary criteria: increased lifespan, amelioration of human aging biomarkers, acceptable toxicity, minimal side effects at therapeutic dosage, improving health-related quality of life. Secondary criteria: evolutionary conservatism of target or mechanism of action, reproducibility of geroprotective effects on different model organisms, simultaneous influence on several aging-associated causes of death in mammals, increase in stress resistance).<ref>Moskalev A, Chernyagina E, Tsvetkov V, Fedintsev A, Shaposhnikov M, Krut'ko V, Zhavoronkov A, Kennedy BK. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016 Jun;15(3):407-15. doi: 10.1111/acel.12463. Epub 2016 Mar 11. PMID: 26970234; PMCID: PMC4854916.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Mechanism ===<br />
According to Knoll's theory, Deprenyl is a catecholaminergic activity enhancer (CAE) and a small daily dose of a CAE is a suitable anti-aging therapy to fight the age-related slow decay of the catecholaminergic system.<ref>Miklya, I. The significance of selegiline/(−)-deprenyl after 50 years in research and therapy (1965–2015). ''Mol Psychiatry'' 21, 1499–1503 (2016). <nowiki>https://doi.org/10.1038/mp.2016.127</nowiki></ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2943Selegiline2023-09-14T10:45:11Z<p>Adssx: /* In humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
In a 2016 study, authors identified deprenyl as one of the 11 compounds (with acarbose, d-glucosamine, dihydroergocristine methanesulfonate, ellagic acid, fenofibrate, glutathione, metformin, spermidine, tyrosol, and vinpocetine) that fulfill all their proposed nine criteria for the evaluation of geroprotectors (Primary criteria: increased lifespan, amelioration of human aging biomarkers, acceptable toxicity, minimal side effects at therapeutic dosage, improving health-related quality of life. Secondary criteria: evolutionary conservatism of target or mechanism of action, reproducibility of geroprotective effects on different model organisms, simultaneous influence on several aging-associated causes of death in mammals, increase in stress resistance).<ref>Moskalev A, Chernyagina E, Tsvetkov V, Fedintsev A, Shaposhnikov M, Krut'ko V, Zhavoronkov A, Kennedy BK. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016 Jun;15(3):407-15. doi: 10.1111/acel.12463. Epub 2016 Mar 11. PMID: 26970234; PMCID: PMC4854916.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Mechanism ===<br />
According to Knoll's theory, Deprenyl is a catecholaminergic activity enhancer (CAE) and a small daily dose of a CAE is a suitable anti-aging therapy to fight the age-related slow decay of the catecholaminergic system.<ref>Miklya, I. The significance of selegiline/(−)-deprenyl after 50 years in research and therapy (1965–2015). ''Mol Psychiatry'' 21, 1499–1503 (2016). <nowiki>https://doi.org/10.1038/mp.2016.127</nowiki></ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2942Selegiline2023-09-14T10:42:25Z<p>Adssx: /* In humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
In a 2016 study, authors identified deprenyl as one of the 11 compounds (with acarbose, d-glucosamine, dihydroergocristine methanesulfonate, ellagic acid, fenofibrate, glutathione, metformin, spermidine, tyrosol, and vinpocetine) that fulfill all their proposed nine criteria for the evaluation of geroprotectors (Primary criteria: increased lifespan, amelioration of human aging biomarkers, acceptable toxicity, minimal side effects at therapeutic dosage, improving health-related quality of life. Secondary criteria: evolutionary conservatism of target or mechanism of action, reproducibility of geroprotective effects on different model organisms, simultaneous influence on several aging-associated causes of death in mammals, increase in stress resistance).<ref>Moskalev A, Chernyagina E, Tsvetkov V, Fedintsev A, Shaposhnikov M, Krut'ko V, Zhavoronkov A, Kennedy BK. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016 Jun;15(3):407-15. doi: 10.1111/acel.12463. Epub 2016 Mar 11. PMID: 26970234; PMCID: PMC4854916.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2941Selegiline2023-09-14T10:25:08Z<p>Adssx: /* In humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
In a 2016 study, authors identified deprenyl as one of the 11 compounds (with acarbose, d-glucosamine, dihydroergocristine methanesulfonate, ellagic acid, fenofibrate, glutathione, metformin, spermidine, tyrosol, and vinpocetine) that fulfill all their proposed nine criteria for the evaluation of geroprotectors (Primary criteria: increased lifespan, amelioration of human aging biomarkers, acceptable toxicity, minimal side effects at therapeutic dosage, improving health-related quality of life. Secondary criteria: evolutionary conservatism of target or mechanism of action, reproducibility of geroprotective effects on different model organisms, simultaneous influence on several aging-associated causes of death in mammals, increase in stress resistance).<ref>Moskalev A, Chernyagina E, Tsvetkov V, Fedintsev A, Shaposhnikov M, Krut'ko V, Zhavoronkov A, Kennedy BK. Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic. Aging Cell. 2016 Jun;15(3):407-15. doi: 10.1111/acel.12463. Epub 2016 Mar 11. PMID: 26970234; PMCID: PMC4854916.</ref><br />
<br />
Increased lifespan Amelioration of human aging biomarkers Acceptable toxicity Minimal side effects at therapeutic dosage Improving health-related quality of life Evolutionary conservatism of target or mechanism of action Reproducibility of geroprotective effects on different model organisms Simultaneous influence on several aging-associated causes of death in mammals Increase in stress resistance.<br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2940Selegiline2023-09-14T10:09:59Z<p>Adssx: /* Mice */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Rodents ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
In Syrian hamsters, low-dose selegiline (0.05 mg/kg) significantly increased life span in females but not in males.<ref>[https://www.sciencedirect.com/science/article/abs/pii/S0197458097000092?via%3Dihub Chronic Treatment of Syrian Hamsters With Low-Dose Selegiline Increases Life Span in Females But Not Males], S. Stoll, U. Hafner, B. Kränzlin, W.E. Müller, Neurobiology of Aging, Volume 18, Issue 2, March–April 1997, Pages 205-211</ref><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2939Selegiline2023-09-14T10:08:22Z<p>Adssx: /* Mice */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Flies ====<br />
Deprenyl led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies.<ref>Jordens, R., Berry, M., Gillott, C. ''et al.'' Prolongation of Life in an Experimental Model of Aging in ''Drosophila Melanogaster'' . ''Neurochem Res'' 24, 227–233 (1999). <nowiki>https://doi.org/10.1023/A:1022510004220</nowiki></ref><br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2938Selegiline2023-09-14T10:06:07Z<p>Adssx: /* Mice */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team at Semmelweis University developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
In 2023, Hungarian researchers from Semmelweis University found that BPAP (a deprenyl derivative) did not improve cognitive performance nor prolong lifespan.<ref>Ernyey, A.J., Kassai, F., Kozma, K. ''et al.'' Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2''R'')-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP). ''GeroScience'' (2023). <nowiki>https://doi.org/10.1007/s11357-023-00821-6</nowiki></ref><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2937Selegiline2023-09-14T10:01:51Z<p>Adssx: /* Dogs */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
One study showed that 1 mg/kg of Deprenyl once daily prolonged life in elderly dogs.<ref>Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF. Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci. 1997;61(11):1037-44. doi: 10.1016/s0024-3205(97)00611-5. PMID: 9307048.</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2936Selegiline2023-09-14T09:57:00Z<p>Adssx: /* Dosage */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended in 1999 "a conservative dose of 5 mg of deprenyl to be taken twice a week".<ref>[https://www.lifeextension.com/magazine/1999/8/qanda Deprenyl], Life Extension Magazine</ref><br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2935Selegiline2023-09-14T09:54:34Z<p>Adssx: /* Dosage */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended Deprenyl in 1996, suggesting total of 5 to 10 mg per week in divided dosages. For instance, Paul Kiesow takes one 5 mg pill broken into four per week.<br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2934Selegiline2023-09-14T09:54:22Z<p>Adssx: /* Dosage */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
Life Extension Foundation (LEF) recommended Deprenyl in 1996 LEF, suggesting total of 5 to 10 mg per week in divided dosages. For instance, Paul Kiesow takes one 5 mg pill broken into four per week.<br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2933Selegiline2023-09-14T09:48:45Z<p>Adssx: /* Notable users */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
Most pills are 5 mg. Knoll suggested 1 mg per day. Late in his life he reportedly took two 5 mg Deprenyl tablets per week.<ref name=":2">[https://www.antiaging-systems.com/articles/deprenyl-a-multi-functional-anti-aging-drug/ Deprenyl- A Multi-Functional Anti-aging Drug], DEAN, M.D., Ward</ref><br />
<br />
LEF suggests a total of 10 mg per week in divided dosages. I follow the LEF protocol and split up two pills in pieces for the week.<br />
<br />
Dean, Fowkes and Morgenthaler recommend the following age-adjusted titrated dosage schedule in their book, ''Smart Drugs 2''. They don't provide scientific evidence for their recommendation:<ref name=":2" /><br />
<br />
* 30–35: 1 mg twice a week<br />
* 35–40: 1 mg every other day<br />
* 40–45: 1 mg every day<br />
* 45–50: 2 mg every day<br />
* 50–55: 3 mg every day<br />
* 55–60: 4 mg every day<br />
* 60–65: 5 mg every day<br />
* 65–70: 6 mg every day<br />
* 70–75: 8 mg every day<br />
* 75–80: 9 mg every day<br />
* 80 and older: 10 mg every day<br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
*[https://www.alldaychemist.com/selgin-5-mg.html#reviews Users reviews on AllDayChemist]<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2932Selegiline2023-09-14T09:41:55Z<p>Adssx: /* Notable users */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://twitter.com/kiesowpaul Paul Kiesow], born in 1952<ref>[https://www.lifeextension.com/magazine/1998/3/profile Not A Bad Place to Be]</ref><br />
*Sam Bankman-Fried, skin patch for depression<ref>[https://slate.com/technology/2022/12/sam-bankman-fried-ftx-emsam-patch-testimony-arrested.html Sam Bankman-Fried Confirmed He Wears an Emsam Patch]. What’s an Emsam Patch?, Slate, HEATHER TAL MURPHY, DEC 14, 2022</ref><br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2931Selegiline2023-09-14T09:40:03Z<p>Adssx: /* Counter indications, risks and side effects */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Notable users ===<br />
<br />
* [https://www.lifeextension.com/magazine/1998/3/profile Paul Kiesow], born 1952<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2930Selegiline2023-09-14T09:38:31Z<p>Adssx: /* In humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> Rasagiline failed to show any cognitive benefits in Parkinson's patients with cognitive impairment. Rasagiline 1 mg has however shown some benefits in a 24-week double-blind parallel group placebo-controlled trial (n=50) with mild to moderate Alzheimer's, with favourable change in FDG-PET in middle frontal, anterior cingulate and striatal regions along with benefits in measures of quality of life.<ref>O’Brien, J.T., Chouliaras, L., Sultana, J. ''et al.'' RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus. ''Alz Res Therapy'' 14, 169 (2022). <nowiki>https://doi.org/10.1186/s13195-022-01103-7</nowiki></ref><br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2929Selegiline2023-09-14T09:36:34Z<p>Adssx: /* Horses */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
==== Horses ====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2928Selegiline2023-09-14T09:35:18Z<p>Adssx: /* In humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
According to Longevity.Technology, Selegiline is at the stage "Late proof of concept demonstrated in real-life conditions"/"Technology refined and ready for initial human trials".<ref>[https://longevity.technology/news/parkinsons-drug-could-revolutionise-longevity-therapies/ Deprenyl Parkinson’s drug increases lifespan in rats], Harriet Grantham, July 10, 2019</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2927Selegiline2023-09-14T09:32:20Z<p>Adssx: /* Dosage */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
=== History ===<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== In humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Combination ===<br />
In experiments with rodents, root extract of ''Polyscias fruticosa'' (also called Ming aralia or by its Vietnamese name Dinh lang) has been demonstrated to extend life span.<ref>Yen, T T; Knoll, J (1991). "Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl". ''Acta Physiologica Hungarica''. '''79''' (2): 119–124. <nowiki>PMID 1304677</nowiki>.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2926Selegiline2023-09-14T09:29:52Z<p>Adssx: /* Counter indications, risks and side effects */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref name=":1">Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /> There's a risk of cheese effect with high doses.<ref name=":1" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2925Selegiline2023-09-14T09:28:32Z<p>Adssx: /* Forms */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
Typical doses for Parkinson's are 10 mg/day (swallowed) or 1.25 mg/day (ODT).<ref>[https://www.drugs.com/dosage/selegiline.html Selegiline Dosage], Drugs.com, Last updated on Aug 10, 2023.</ref><br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2924Selegiline2023-09-14T09:26:57Z<p>Adssx: /* Counter indications, risks and side effects */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /> In particular, Selegiline should not be taken by individuals with liver or kidney disease, high blood pressure, or phenylketonuria. Additionally, you should not take it if you have taken fluoxetine within the past five weeks. It should also not be taken with cough medicines that contain dextromethorphan, cyclobenzaprine (Flexeril), meperidine or any other opioid pain medicine, methadone, St. John’s wort, tramadol (Ultram), any antidepressants or MAO inhibitors.<ref name=":0" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2923Selegiline2023-09-14T09:26:02Z<p>Adssx: /* Mice */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and a Japanese group led by Kenichi Kitani of the National Institute for Longevity Sciences (NILS) of Japan. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
Kitani reported an inverted U-shape dose-relationship effect on the expression of uperoxide dismutase 1 (SOD1) and catalase in the striatum of rats.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. It is given at doeses of 0.5mg/kg/day.<ref name=":0" /> Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2922Selegiline2023-09-14T09:21:36Z<p>Adssx: /* Mice */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /> Life extension ranged from no change (4 studies), to slight single-digit increases (2 studies), to increases between 13%-24% (2 studies), to increases in lifespan above 30% (2 studies). Most of these studies come from Knoll and another Japanese group. The greatest increases in lifespan were seen in doses of 0.25mg/kg, 3 times per week.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2921Selegiline2023-09-14T09:17:42Z<p>Adssx: /* Humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> Selegiline + levodopa has been reported to increase, decrease, or have no change in lifespan of Parkinson's compared to levodopa alone.<ref name=":0" /> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2920Selegiline2023-09-14T08:57:49Z<p>Adssx: /* Mice */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rodents, Selegiline has been reported to increase, decrease, or have no change in lifespan in animal models. The mechanism for an increase in lifespan is unclear.<ref name=":0" /><br />
<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2919Selegiline2023-09-14T08:57:14Z<p>Adssx: /* Counter indications, risks and side effects */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref name=":0">[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
According to the ADDF: "Despite the potential for some side-effects, these are generally not serious. However, there are many potential drug interactions."<ref name=":0" /><br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2918Selegiline2023-09-14T08:56:35Z<p>Adssx: /* Humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
According to a 2018 review by the Alzheimer’s Drug Discovery Foundation (ADDF): "Selegiline may provide a small, though possibly not clinically meaningful, benefit for Alzheimer’s disease; the longevity research is mixed."<ref>[https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Selegiline-Cognitive-Vitality-For-Researchers.pdf Selegiline (L-deprenyl)], Cognitive Vitality Report, Alzheimer’s Drug Discovery Foundation, May 14th 2018</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2917Selegiline2023-09-14T08:55:00Z<p>Adssx: /* Mice */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
In rat models of Parkinson's disease, Selegiline delayed α-syn aggregation and dopaminergic neuronal loss.<ref>Nakamura Y, Arawaka S, Sato H, Sasaki A, Shigekiyo T, Takahata K, Tsunekawa H, Kato T. Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion ''In Vitro'' and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease. J Neurosci. 2021 Sep 1;41(35):7479-7491. doi: 10.1523/JNEUROSCI.0476-21.2021. Epub 2021 Jul 21. PMID: 34290084; PMCID: PMC8412984.</ref><br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2916Selegiline2023-09-14T08:49:08Z<p>Adssx: /* Humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
Rasagiline, another irreversible inhibitor of monoamine oxidase-B used in Parkinson's disease, may also be neuroprotective. The FDA refused to grant disease-modifying label to rasagiline because in trials the lower dose was effective at slowing progression, but the higher dose was not.<ref>Sviderski V (19 October 2011). "FDA Advisers Refuse Teva Plea to Expand Azilect Label". ''Reuters and Haaretz''.</ref><ref>Katz R, et al. "Peripheral and Central Nervous System Advisory Committee Background Package on Azilect" (PDF). FDA. Retrieved December 7, 2011.</ref> However, studies in mice also found an inverted U-shape dose-response relationship curve for selegiline.<br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2915Selegiline2023-09-14T08:44:34Z<p>Adssx: /* Humans */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis.<ref>Riederer P, Lachenmayer L (November 2003). "Selegiline's neuroprotective capacity revisited". ''Journal of Neural Transmission''. '''110''' (11): 1273–1278. doi:10.1007/s00702-003-0083-x. <nowiki>PMID 14628191</nowiki>. S2CID 20232921.</ref> There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<ref>"Selegiline Hydrochloride Monograph for Professionals". ''Drugs.com''. Retrieved February 23, 2018.</ref><ref>Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004). "Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients". ''BMJ''. '''329''' (7466): 593. doi:10.1136/bmj.38184.606169.AE. PMC 516655. <nowiki>PMID 15310558</nowiki>.</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2914Selegiline2023-09-14T08:43:47Z<p>Adssx: /* Life extension */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Humans ===<br />
In Parkinson's patients, Selegiline delays the point when levodopa treatment becomes necessary from about 11 months to about 18 months after diagnosis. There is some evidence that selegiline acts as a neuroprotectant and reduces the rate of disease progression, though this is disputed.<br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Counter indications, risks and side effects ===<br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2913Selegiline2023-09-14T08:41:35Z<p>Adssx: /* Dosage */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Animal studies ===<br />
<br />
==== Mice ====<br />
<br />
==== Dogs ====<br />
Selegiline is approved to treat canine cognitive dysfunction, a form of dementia that mimics Alzheimer's disease in humans. Geriatric dogs treated with selegiline show improvements in sleeping pattern, reduced incontinence, and increased activity level; most show improvements by one month. Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.<ref>[https://www.drugs.com/vet/anipryl-tablets.html Anipryl Tablets]</ref><br />
<br />
==== Cats ====<br />
Selegiline is also used off-label for geriatric cats with cognitive dysfunction.<ref>Riviere JE, Papich MG (2013). ''Veterinary Pharmacology and Therapeutics''. John Wiley & Sons. p. 530. ISBN <bdi>978-1-118-68590-7</bdi>.</ref><br />
<br />
===== Horses =====<br />
Selegiline does not appear to have a clinical effect on horses, although it hasn't been studied specifically for longevity on horses.<ref>Papich MG (2015). ''Saunders Handbook of Veterinary Drugs: Small and Large Animal''. Elsevier Health Sciences. p. 722. ISBN <bdi>978-0-323-24485-5</bdi>.</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2912Selegiline2023-09-14T08:36:46Z<p>Adssx: /* Forms */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Forms ===<br />
Selegiline is commercially available under three forms:<br />
<br />
* Capsule or tablet taken by mouth (to swallow), sold under various brand names and also available in generics.<br />
* Orally disintegrating tablets (to dissolve on the tongue) also called ODT. Sold under the brand name Zelapar and not available in generic as of 2023.<ref>[https://www.drugs.com/availability/generic-zelapar.html Generic Zelapar Availability - Drugs.com]</ref> Flavored (grapefruit) and sweetened. Mainly used by Parkinson's patients with swallowing difficulties who need high doses.<br />
* Transdermal patch (to apply on the skin), mainly used for depression.<br />
<br />
<br />
The ODT is about 10 times more potent than the normal tablet.<ref>Tábi, T., Vécsei, L., Youdim, M.B. ''et al.'' [https://doi.org/10.1007/s00702-019-02082-0 Selegiline: a molecule with innovative potential]. ''J Neural Transm'' '''127''', 831–842 (2020).</ref> Only the normal tablet (swallowed) has been studied for its life extension properties.<br />
<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2911Selegiline2023-09-14T08:29:12Z<p>Adssx: /* Life extension */</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
=== Forms ===<br />
=== Dosage ===<br />
<br />
== References ==<br />
<references /></div>Adssxhttps://en.longevitywiki.org/index.php?title=Selegiline&diff=2910Selegiline2023-09-14T08:28:34Z<p>Adssx: Created page with "'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''. == Life extension == Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of t..."</p>
<hr />
<div>'''Selegiline''', also known as '''Deprenyl''' and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. For basic information, see '''Wikipedia'''.<br />
<br />
== Life extension ==<br />
Hungarian Joseph Knoll and his team developed selegiline and explored it potential longevity enhancing effects of selegiline up until his death in 2018 at age 93. Knoll was the founding member of the Hungarian Society for Experimental and Clinical Pharmacology and until 1982 its president and then honorary life president. Between 1984 and 1987 he was the first vice-president of the board of the Executive Committee of the International Union of Pharmacology (IUPHAR).<ref>[https://huphar.org/en/in-memoriam-joseph-knoll-1925-2018/ IN MEMORIAM JOSEPH KNOLL (1925-2018)], Hungarian Society for Experimental and Clinical Pharmacology</ref><br />
<br />
== References ==<br />
<references /></div>Adssx