Calcium channel blockers (CCBs) - Revision history

Dmitry Dzhagarov: /* Cinnarizine */

2024-09-21T12:36:44Z

Cinnarizine

← Older revision		Revision as of 12:36, 21 September 2024
Line 53:		Line 53:
	== Cinnarizine ==		== Cinnarizine ==
	Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. Cinnarizine is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome, also as a nootropic drug (memory and cognitive function enhancer) and as adjunct therapy for peripheral arterial disease.<ref>Kirtane, M. V., Bhandari, A., Narang, P., & Santani, R. (2019). Cinnarizine: a contemporary review. Indian Journal of Otolaryngology and Head & Neck Surgery, 71, 1060-1068. PMID: 31750127 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841794/ PMC6841794] DOI: 10.1007/s12070-017-1120-7</ref> As a selective calcium channel blocker (SCCB), it reduces the entry of Ca2+ ions into cells and decreases their concentration in the plasma membrane depot, reduces the tone of the smooth muscles of arterioles, and enhances the vasodilating effect of carbon dioxide.		Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. Cinnarizine is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome, also as a nootropic drug (memory and cognitive function enhancer) and as adjunct therapy for peripheral arterial disease.<ref>Kirtane, M. V., Bhandari, A., Narang, P., & Santani, R. (2019). Cinnarizine: a contemporary review. Indian Journal of Otolaryngology and Head & Neck Surgery, 71, 1060-1068. PMID: 31750127 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841794/ PMC6841794] DOI: 10.1007/s12070-017-1120-7</ref> As a selective calcium channel blocker (SCCB), it reduces the entry of Ca2+ ions into cells and decreases their concentration in the plasma membrane depot, reduces the tone of the smooth muscles of arterioles, and enhances the vasodilating effect of carbon dioxide.
	Сinnarizine dose-dependently inhibits the mammalian target of rapamycin (mTOR), and selectively mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2), which allows cinnarizine to be classified as an mTOR inhibitor (rapalog) that is a geroprotector.<ref>Allen, S. A., Tomilov, A., & Cortopassi, G. A. (2018). Small molecules bind human mTOR protein and inhibit mTORC1 specifically. Biochemical pharmacology, 155, 298-304. PMID 30028993 doi:10.1016/j.bcp.2018.07.013</ref><ref>Dumas, S. N., & Lamming, D. W. (2020). Next generation strategies for geroprotection via mTORC1 inhibition. The Journals of Gerontology: Series A, 75(1), 14-23. PMID 30794726 PMC 6909887 doi:10.1093/gerona/glz056</ref>		Сinnarizine dose-dependently inhibits the mammalian target of rapamycin (mTOR), and selectively mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2), which allows cinnarizine to be classified as an mTOR inhibitor (rapalog) that is a geroprotector.<ref>Allen, S. A., Tomilov, A., & Cortopassi, G. A. (2018). Small molecules bind human mTOR protein and inhibit mTORC1 specifically. Biochemical pharmacology, 155, 298-304. PMID 30028993 doi:10.1016/j.bcp.2018.07.013</ref>

	Chronic administration of the calcium channel blocker cinnarizine to senescent animals with significant aging-induced decreased density of dopamine D2 and especially D1 receptors, regain these pathological disorders.<ref>Camps, M., Ambrosio, S., Reiriz, J., Ballarin, M., Cutillas, B., & Mahy, N. (1993). Effect of age and cinnarizine treatment on brain dopamine receptors. Pharmacology, 46(1), 9-12. PMID: 8434032 DOI: 10.1159/000139023</ref>		Chronic administration of the calcium channel blocker cinnarizine to senescent animals with significant aging-induced decreased density of dopamine D2 and especially D1 receptors, regain these pathological disorders.<ref>Camps, M., Ambrosio, S., Reiriz, J., Ballarin, M., Cutillas, B., & Mahy, N. (1993). Effect of age and cinnarizine treatment on brain dopamine receptors. Pharmacology, 46(1), 9-12. PMID: 8434032 DOI: 10.1159/000139023</ref>

Dmitry Dzhagarov at 21:01, 28 August 2024

2024-08-28T21:01:47Z

@@ Line 1: / Line 1: @@
-'''Calcium channel blockers (CCBs)''' use was associated with a 70% lower risk for frailty (95%CI = 0.09 to 0.77).<ref>Chuang, S. Y., Pan, W. H., Chang, H. Y., Wu, C. I., Chen, C. Y., & Hsu, C. C. (2016). Protective effect of calcium channel blockers against frailty in older adults with hypertension. Journal of the American Geriatrics Society, 64(6), 1356-1358.</ref>
+'''Calcium channel blockers (CCBs)''' use was associated with a 70% lower risk for frailty (95%CI = 0.09 to 0.77).<ref>Chuang, S. Y., Pan, W. H., Chang, H. Y., Wu, C. I., Chen, C. Y., & Hsu, C. C. (2016). Protective effect of calcium channel blockers against frailty in older adults with hypertension. Journal of the American Geriatrics Society, 64(6), 1356-1358.</ref>  The use of CCBs in 75+ y.o. patients with renovascular disease. was associated with a significant reduction in overall mortality and cardiovascular death.<ref>Deshmukh, H., Barker, E., Anbarasan, T., Levin, D., Bell, S., Witham, M. D., & George, J. (2018). Calcium channel blockers are associated with improved survival and lower cardiovascular mortality in patients with renovascular disease. Cardiovascular Therapeutics, 36(6), e12474. PMID: 30372589 DOI: 10.1111/1755-5922.12474</ref>
 The point estimates for  calcium channel blockers (CCBs) indicated a decrease in seven [[Epigenetic clock|DNAmAges]] (a decrease of 0.57 to 1.74 years in five PCDNAmAges, a 0.03-year decrease of aging rate in DunedinPACE, and an elongation of 0.01 in PCDNAmTL), among which the estimates for PCHorvathAge (beta = − 1.28, 95%CI = − 2.34 to − 0.21), PCSkin&bloodAge (beta = − 1.34, 95%CI = − 2.61 to − 0.07), PCPhenoAge (beta = − 1.74, 95%CI = − 2.58 to − 0.89), and PCGrimAge (beta = − 0.57, 95%CI = − 0.96 to − 0.17) excluded the null. In addition to DNAmAges, CCBs was also associated with decreased functional biological ages, shown in FAI (beta = − 2.18, 95%CI = − 3.65 to − 0.71) and FI (beta = − 1.31, 95%CI = − 2.43 to − 0.18).<ref>Tang, B., Li, X., Wang, Y., Sjölander, A., Johnell, K., Thambisetty, M., ... & Hägg, S. (2023). Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging. GeroScience, 45(3), 2065-2078. PMID: 37032369 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400489/ PMC10400489] DOI: 10.1007/s11357-023-00784-8</ref>
 Patients with hypertension who were treated with calcium channel blocker (CCB), but not in diuretics demonstrated an association between telomere attrition rate and the differences in antihypertensive treatment response - their analyzes showed that the increase of leukocyte telomere length is associated with the decrease of systolic blood pressure and pulse pressure.<ref>Zhang, S. Y., Li, R. X., Yang, Y. Y., Chen, Y., Yang, S. J., Li, J., ... & Zhang, W. L. (2019). P1693 The longitudinal associations between telomere attrition and the effects of blood pressure lowering and antihypertensive treatment. European Heart Journal, 40(Supplement_1), ehz748-0448.   https://doi.org/10.1093/eurheartj/ehz748.0448</ref>
 == Verapamil ==

Dmitry Dzhagarov: /* Cinnarizine */

2024-08-15T16:14:36Z

Cinnarizine

← Older revision		Revision as of 16:14, 15 August 2024
Line 10:		Line 10:

	== Cinnarizine ==		== Cinnarizine ==
	Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. Cinnarizine is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome. As a selective calcium channel blocker (SCCB), it reduces the entry of Ca2+ ions into cells and decreases their concentration in the plasma membrane depot, reduces the tone of the smooth muscles of arterioles, and enhances the vasodilating effect of carbon dioxide.		Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. Cinnarizine is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome, also as a nootropic drug (memory and cognitive function enhancer) and as adjunct therapy for peripheral arterial disease.<ref>Kirtane, M. V., Bhandari, A., Narang, P., & Santani, R. (2019). Cinnarizine: a contemporary review. Indian Journal of Otolaryngology and Head & Neck Surgery, 71, 1060-1068. PMID: 31750127 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841794/ PMC6841794] DOI: 10.1007/s12070-017-1120-7</ref> As a selective calcium channel blocker (SCCB), it reduces the entry of Ca2+ ions into cells and decreases their concentration in the plasma membrane depot, reduces the tone of the smooth muscles of arterioles, and enhances the vasodilating effect of carbon dioxide.
	Сinnarizine dose-dependently inhibits the mammalian target of rapamycin (mTOR), and selectively mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2), which allows cinnarizine to be classified as an mTOR inhibitor (rapalog) that is a geroprotector.<ref>Allen, S. A., Tomilov, A., & Cortopassi, G. A. (2018). Small molecules bind human mTOR protein and inhibit mTORC1 specifically. Biochemical pharmacology, 155, 298-304. PMID 30028993 doi:10.1016/j.bcp.2018.07.013</ref><ref>Dumas, S. N., & Lamming, D. W. (2020). Next generation strategies for geroprotection via mTORC1 inhibition. The Journals of Gerontology: Series A, 75(1), 14-23. PMID 30794726 PMC 6909887 doi:10.1093/gerona/glz056</ref>		Сinnarizine dose-dependently inhibits the mammalian target of rapamycin (mTOR), and selectively mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2), which allows cinnarizine to be classified as an mTOR inhibitor (rapalog) that is a geroprotector.<ref>Allen, S. A., Tomilov, A., & Cortopassi, G. A. (2018). Small molecules bind human mTOR protein and inhibit mTORC1 specifically. Biochemical pharmacology, 155, 298-304. PMID 30028993 doi:10.1016/j.bcp.2018.07.013</ref><ref>Dumas, S. N., & Lamming, D. W. (2020). Next generation strategies for geroprotection via mTORC1 inhibition. The Journals of Gerontology: Series A, 75(1), 14-23. PMID 30794726 PMC 6909887 doi:10.1093/gerona/glz056</ref>

Dmitry Dzhagarov: /* Cinnarizine */

2024-08-15T13:38:15Z

Cinnarizine

← Older revision		Revision as of 13:38, 15 August 2024
Line 12:		Line 12:
	Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. Cinnarizine is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome. As a selective calcium channel blocker (SCCB), it reduces the entry of Ca2+ ions into cells and decreases their concentration in the plasma membrane depot, reduces the tone of the smooth muscles of arterioles, and enhances the vasodilating effect of carbon dioxide.		Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. Cinnarizine is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome. As a selective calcium channel blocker (SCCB), it reduces the entry of Ca2+ ions into cells and decreases their concentration in the plasma membrane depot, reduces the tone of the smooth muscles of arterioles, and enhances the vasodilating effect of carbon dioxide.
	Сinnarizine dose-dependently inhibits the mammalian target of rapamycin (mTOR), and selectively mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2), which allows cinnarizine to be classified as an mTOR inhibitor (rapalog) that is a geroprotector.<ref>Allen, S. A., Tomilov, A., & Cortopassi, G. A. (2018). Small molecules bind human mTOR protein and inhibit mTORC1 specifically. Biochemical pharmacology, 155, 298-304. PMID 30028993 doi:10.1016/j.bcp.2018.07.013</ref><ref>Dumas, S. N., & Lamming, D. W. (2020). Next generation strategies for geroprotection via mTORC1 inhibition. The Journals of Gerontology: Series A, 75(1), 14-23. PMID 30794726 PMC 6909887 doi:10.1093/gerona/glz056</ref>		Сinnarizine dose-dependently inhibits the mammalian target of rapamycin (mTOR), and selectively mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2), which allows cinnarizine to be classified as an mTOR inhibitor (rapalog) that is a geroprotector.<ref>Allen, S. A., Tomilov, A., & Cortopassi, G. A. (2018). Small molecules bind human mTOR protein and inhibit mTORC1 specifically. Biochemical pharmacology, 155, 298-304. PMID 30028993 doi:10.1016/j.bcp.2018.07.013</ref><ref>Dumas, S. N., & Lamming, D. W. (2020). Next generation strategies for geroprotection via mTORC1 inhibition. The Journals of Gerontology: Series A, 75(1), 14-23. PMID 30794726 PMC 6909887 doi:10.1093/gerona/glz056</ref>

			Chronic administration of the calcium channel blocker cinnarizine to senescent animals with significant aging-induced decreased density of dopamine D2 and especially D1 receptors, regain these pathological disorders.<ref>Camps, M., Ambrosio, S., Reiriz, J., Ballarin, M., Cutillas, B., & Mahy, N. (1993). Effect of age and cinnarizine treatment on brain dopamine receptors. Pharmacology, 46(1), 9-12. PMID: 8434032 DOI: 10.1159/000139023</ref>

	== Fasudil ==		== Fasudil ==

Dmitry Dzhagarov: /* Verapamil */

2024-08-11T13:28:49Z

Verapamil

← Older revision		Revision as of 13:28, 11 August 2024
Line 6:		Line 6:

	== Verapamil ==		== Verapamil ==
			(also: nifedipine, amlodipine, lacidipine, nicardipine)
	Verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity.<ref>Liu, W., Lin, H., Mao, Z., Zhang, L., Bao, K., Jiang, B., ... & Li, J. (2020). Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy. Aging (Albany NY), 12(6), 5300. PMID: 32208362 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138547 PMC7138547] DOI: 10.18632/aging.102951</ref>		Verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity.<ref>Liu, W., Lin, H., Mao, Z., Zhang, L., Bao, K., Jiang, B., ... & Li, J. (2020). Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy. Aging (Albany NY), 12(6), 5300. PMID: 32208362 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138547 PMC7138547] DOI: 10.18632/aging.102951</ref>

			== Cinnarizine ==
			Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. Cinnarizine is predominantly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménière's disease, or Cogan's syndrome. As a selective calcium channel blocker (SCCB), it reduces the entry of Ca2+ ions into cells and decreases their concentration in the plasma membrane depot, reduces the tone of the smooth muscles of arterioles, and enhances the vasodilating effect of carbon dioxide.
			Сinnarizine dose-dependently inhibits the mammalian target of rapamycin (mTOR), and selectively mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2), which allows cinnarizine to be classified as an mTOR inhibitor (rapalog) that is a geroprotector.<ref>Allen, S. A., Tomilov, A., & Cortopassi, G. A. (2018). Small molecules bind human mTOR protein and inhibit mTORC1 specifically. Biochemical pharmacology, 155, 298-304. PMID 30028993 doi:10.1016/j.bcp.2018.07.013</ref><ref>Dumas, S. N., & Lamming, D. W. (2020). Next generation strategies for geroprotection via mTORC1 inhibition. The Journals of Gerontology: Series A, 75(1), 14-23. PMID 30794726 PMC 6909887 doi:10.1093/gerona/glz056</ref>

	== Fasudil ==		== Fasudil ==

Dmitry Dzhagarov at 09:47, 29 July 2024

2024-07-29T09:47:20Z

← Older revision		Revision as of 09:47, 29 July 2024
Line 1:		Line 1:
	'''Calcium channel blockers (CCBs)''' use was associated with a 70% lower risk for frailty (95%CI = 0.09 to 0.77).<ref>Chuang, S. Y., Pan, W. H., Chang, H. Y., Wu, C. I., Chen, C. Y., & Hsu, C. C. (2016). Protective effect of calcium channel blockers against frailty in older adults with hypertension. Journal of the American Geriatrics Society, 64(6), 1356-1358.</ref>		'''Calcium channel blockers (CCBs)''' use was associated with a 70% lower risk for frailty (95%CI = 0.09 to 0.77).<ref>Chuang, S. Y., Pan, W. H., Chang, H. Y., Wu, C. I., Chen, C. Y., & Hsu, C. C. (2016). Protective effect of calcium channel blockers against frailty in older adults with hypertension. Journal of the American Geriatrics Society, 64(6), 1356-1358.</ref>

	The point estimates for calcium channel blockers (CCBs) indicated a decrease in seven [[Epigenetic clock\|DNAmAges]] (a decrease of 0.57 to 1.74 years in five PCDNAmAges, a 0.03-year decrease of aging rate in DunedinPACE, and an elongation of 0.01 in PCDNAmTL), among which the estimates for PCHorvathAge (beta = − 1.28, 95%CI = − 2.34 to − 0.21), PCSkin&bloodAge (beta = − 1.34, 95%CI = − 2.61 to − 0.07), PCPhenoAge (beta = − 1.74, 95%CI = − 2.58 to − 0.89), and PCGrimAge (beta = − 0.57, 95%CI = − 0.96 to − 0.17) excluded the null. In addition to DNAmAges, CCBs was also associated with decreased functional biological ages, shown in FAI (beta = − 2.18, 95%CI = − 3.65 to − 0.71) and FI (beta = − 1.31, 95%CI = − 2.43 to − 0.18).<ref>Tang, B., Li, X., Wang, Y., Sjölander, A., Johnell, K., Thambisetty, M., ... & Hägg, S. (2023). Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging. GeroScience, 45(3), 2065-2078. PMID: 37032369 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400489/ PMC10400489] DOI: 10.1007/s11357-023-00784-8</ref>		The point estimates for calcium channel blockers (CCBs) indicated a decrease in seven [[Epigenetic clock\|DNAmAges]] (a decrease of 0.57 to 1.74 years in five PCDNAmAges, a 0.03-year decrease of aging rate in DunedinPACE, and an elongation of 0.01 in PCDNAmTL), among which the estimates for PCHorvathAge (beta = − 1.28, 95%CI = − 2.34 to − 0.21), PCSkin&bloodAge (beta = − 1.34, 95%CI = − 2.61 to − 0.07), PCPhenoAge (beta = − 1.74, 95%CI = − 2.58 to − 0.89), and PCGrimAge (beta = − 0.57, 95%CI = − 0.96 to − 0.17) excluded the null. In addition to DNAmAges, CCBs was also associated with decreased functional biological ages, shown in FAI (beta = − 2.18, 95%CI = − 3.65 to − 0.71) and FI (beta = − 1.31, 95%CI = − 2.43 to − 0.18).<ref>Tang, B., Li, X., Wang, Y., Sjölander, A., Johnell, K., Thambisetty, M., ... & Hägg, S. (2023). Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging. GeroScience, 45(3), 2065-2078. PMID: 37032369 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400489/ PMC10400489] DOI: 10.1007/s11357-023-00784-8</ref>

			Patients with hypertension who were treated with calcium channel blocker (CCB), but not in diuretics demonstrated an association between telomere attrition rate and the differences in antihypertensive treatment response - their analyzes showed that the increase of leukocyte telomere length is associated with the decrease of systolic blood pressure and pulse pressure.<ref>Zhang, S. Y., Li, R. X., Yang, Y. Y., Chen, Y., Yang, S. J., Li, J., ... & Zhang, W. L. (2019). P1693 The longitudinal associations between telomere attrition and the effects of blood pressure lowering and antihypertensive treatment. European Heart Journal, 40(Supplement_1), ehz748-0448. https://doi.org/10.1093/eurheartj/ehz748.0448</ref>

	== Verapamil ==		== Verapamil ==

Dmitry Dzhagarov at 17:38, 28 July 2024

2024-07-28T17:38:36Z

← Older revision		Revision as of 17:38, 28 July 2024
Line 1:		Line 1:
	'''Calcium channel blockers (CCBs)''' use was associated with a 70% lower risk for frailty (95%CI = 0.09 to 0.77).<ref>Chuang, S. Y., Pan, W. H., Chang, H. Y., Wu, C. I., Chen, C. Y., & Hsu, C. C. (2016). Protective effect of calcium channel blockers against frailty in older adults with hypertension. Journal of the American Geriatrics Society, 64(6), 1356-1358.</ref>		'''Calcium channel blockers (CCBs)''' use was associated with a 70% lower risk for frailty (95%CI = 0.09 to 0.77).<ref>Chuang, S. Y., Pan, W. H., Chang, H. Y., Wu, C. I., Chen, C. Y., & Hsu, C. C. (2016). Protective effect of calcium channel blockers against frailty in older adults with hypertension. Journal of the American Geriatrics Society, 64(6), 1356-1358.</ref>

	The point estimates for calcium channel blockers (CCBs) indicated a decrease in seven DNAmAges (a decrease of 0.57 to 1.74 years in five PCDNAmAges, a 0.03-year decrease of aging rate in DunedinPACE, and an elongation of 0.01 in PCDNAmTL), among which the estimates for PCHorvathAge (beta = − 1.28, 95%CI = − 2.34 to − 0.21), PCSkin&bloodAge (beta = − 1.34, 95%CI = − 2.61 to − 0.07), PCPhenoAge (beta = − 1.74, 95%CI = − 2.58 to − 0.89), and PCGrimAge (beta = − 0.57, 95%CI = − 0.96 to − 0.17) excluded the null. In addition to DNAmAges, CCBs was also associated with decreased functional biological ages, shown in FAI (beta = − 2.18, 95%CI = − 3.65 to − 0.71) and FI (beta = − 1.31, 95%CI = − 2.43 to − 0.18).<ref>Tang, B., Li, X., Wang, Y., Sjölander, A., Johnell, K., Thambisetty, M., ... & Hägg, S. (2023). Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging. GeroScience, 45(3), 2065-2078. PMID: 37032369 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400489/ PMC10400489] DOI: 10.1007/s11357-023-00784-8</ref>		The point estimates for calcium channel blockers (CCBs) indicated a decrease in seven [[Epigenetic clock\|DNAmAges]] (a decrease of 0.57 to 1.74 years in five PCDNAmAges, a 0.03-year decrease of aging rate in DunedinPACE, and an elongation of 0.01 in PCDNAmTL), among which the estimates for PCHorvathAge (beta = − 1.28, 95%CI = − 2.34 to − 0.21), PCSkin&bloodAge (beta = − 1.34, 95%CI = − 2.61 to − 0.07), PCPhenoAge (beta = − 1.74, 95%CI = − 2.58 to − 0.89), and PCGrimAge (beta = − 0.57, 95%CI = − 0.96 to − 0.17) excluded the null. In addition to DNAmAges, CCBs was also associated with decreased functional biological ages, shown in FAI (beta = − 2.18, 95%CI = − 3.65 to − 0.71) and FI (beta = − 1.31, 95%CI = − 2.43 to − 0.18).<ref>Tang, B., Li, X., Wang, Y., Sjölander, A., Johnell, K., Thambisetty, M., ... & Hägg, S. (2023). Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging. GeroScience, 45(3), 2065-2078. PMID: 37032369 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400489/ PMC10400489] DOI: 10.1007/s11357-023-00784-8</ref>

	== Verapamil ==		== Verapamil ==

Dmitry Dzhagarov: /* Fasudil */

2024-06-28T14:19:37Z

Fasudil

← Older revision		Revision as of 14:19, 28 June 2024
Line 10:		Line 10:

	Despite its successful introduction into clinical practice in Japan and China for almost 30 years, the use of fasudil in other countries faces certain limitations. Although fasudil inhibits both ROCK isoforms (ROCK1 and ROCK2) more potently than other kinases, some of its side effects, including hypotension, skin reactions and reversible renal dysfunction, are major barriers to its widespread use.<ref>Wolff, A. W., Peine, J., Höfler, J., Zurek, G., Hemker, C., & Lingor, P. (2024). SAFE-ROCK: A Phase I Trial of an Oral Application of the ROCK Inhibitor Fasudil to Assess Bioavailability, Safety, and Tolerability in Healthy Participants. CNS drugs, 38(4), 291-302. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980656/ PMC10980656]</ref>		Despite its successful introduction into clinical practice in Japan and China for almost 30 years, the use of fasudil in other countries faces certain limitations. Although fasudil inhibits both ROCK isoforms (ROCK1 and ROCK2) more potently than other kinases, some of its side effects, including hypotension, skin reactions and reversible renal dysfunction, are major barriers to its widespread use.<ref>Wolff, A. W., Peine, J., Höfler, J., Zurek, G., Hemker, C., & Lingor, P. (2024). SAFE-ROCK: A Phase I Trial of an Oral Application of the ROCK Inhibitor Fasudil to Assess Bioavailability, Safety, and Tolerability in Healthy Participants. CNS drugs, 38(4), 291-302. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980656/ PMC10980656]</ref>

			== References ==
			<references />

	[[Category:Drugs]]		[[Category:Drugs]]
	[[Category:Lifespan interventions]]		[[Category:Lifespan interventions]]
	[[Category:Main list]]		[[Category:Main list]]

Dmitry Dzhagarov: /* Fasudil */

2024-06-28T14:16:35Z

Fasudil

← Older revision		Revision as of 14:16, 28 June 2024
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	The small molecule fasudil, formerly known as HA1077 or AT‐877, is the ROCK inhibitor that has been used in Japan and China since 1995 for the treatment of vasospasms following subarachnoid haemorrhage, as well as to prevent the loss of intelligence and memory observed in stroke patients and the elderly.<ref>Suzuki, Y., Shibuya, M., Satoh, S. I., Sugimoto, Y., & Takakura, K. (2007). A postmarketing surveillance study of fasudil treatment after aneurysmal subarachnoid hemorrhage. Surgical neurology, 68(2), 126-131. PMID: 17586012 DOI: 10.1016/j.surneu.2006.10.037</ref> Fasudil also could ameliorate impairments in skeletal muscle blood flow observed in older adults<ref>Darvish, S., Coppock, M. E., & Murray, K. O. (2022). Age-related impairments in ATP release by red blood cells as an important contributor to declines in skeletal muscle blood flow in older adults. The Journal of physiology, 600(16), 3643. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378623/ PMC9378623]</ref> It is marketed under the name ERIL®. It was initially characterized as a calcium antagonist, different from previously known calcium channel blockers such as verapamil, diltiazem and nicardipine in that it could prevent arterial contraction in conditions where other calcium channel blockers had failed.<ref>Asano, T. O., Ikegaki, I. C., Satoh, S.,et al., & Hidaka, H. (1987). Mechanism of action of a novel antivasospasm drug, HA1077. Journal of Pharmacology and Experimental Therapeutics, 241(3), 1033-1040. PMID 3598899</ref>		The small molecule fasudil, formerly known as HA1077 or AT‐877, is the ROCK inhibitor that has been used in Japan and China since 1995 for the treatment of vasospasms following subarachnoid haemorrhage, as well as to prevent the loss of intelligence and memory observed in stroke patients and the elderly.<ref>Suzuki, Y., Shibuya, M., Satoh, S. I., Sugimoto, Y., & Takakura, K. (2007). A postmarketing surveillance study of fasudil treatment after aneurysmal subarachnoid hemorrhage. Surgical neurology, 68(2), 126-131. PMID: 17586012 DOI: 10.1016/j.surneu.2006.10.037</ref> Fasudil also could ameliorate impairments in skeletal muscle blood flow observed in older adults<ref>Darvish, S., Coppock, M. E., & Murray, K. O. (2022). Age-related impairments in ATP release by red blood cells as an important contributor to declines in skeletal muscle blood flow in older adults. The Journal of physiology, 600(16), 3643. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378623/ PMC9378623]</ref> It is marketed under the name ERIL®. It was initially characterized as a calcium antagonist, different from previously known calcium channel blockers such as verapamil, diltiazem and nicardipine in that it could prevent arterial contraction in conditions where other calcium channel blockers had failed.<ref>Asano, T. O., Ikegaki, I. C., Satoh, S.,et al., & Hidaka, H. (1987). Mechanism of action of a novel antivasospasm drug, HA1077. Journal of Pharmacology and Experimental Therapeutics, 241(3), 1033-1040. PMID 3598899</ref>

	Despite its successful introduction into clinical practice in Japan and China for almost 30 years, the use of fasudil in other countries faces certain limitations. Although fasudil inhibits both ROCK isoforms (ROCK1 and ROCK2) more potently than other kinases, some of its side effects, including hypotension, skin reactions and reversible renal dysfunction, are major barriers to its widespread use.<ref>Wolff, A. W., Peine, J., Höfler, J., Zurek, G., Hemker, C., & Lingor, P. (2024). SAFE-ROCK: A Phase I Trial of an Oral Application of the ROCK Inhibitor Fasudil to Assess Bioavailability, Safety, and Tolerability in Healthy Participants. CNS drugs, 38(4), 291-302. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980656/ PMC10980656]~~</ref><ref>~~</ref>		Despite its successful introduction into clinical practice in Japan and China for almost 30 years, the use of fasudil in other countries faces certain limitations. Although fasudil inhibits both ROCK isoforms (ROCK1 and ROCK2) more potently than other kinases, some of its side effects, including hypotension, skin reactions and reversible renal dysfunction, are major barriers to its widespread use.<ref>Wolff, A. W., Peine, J., Höfler, J., Zurek, G., Hemker, C., & Lingor, P. (2024). SAFE-ROCK: A Phase I Trial of an Oral Application of the ROCK Inhibitor Fasudil to Assess Bioavailability, Safety, and Tolerability in Healthy Participants. CNS drugs, 38(4), 291-302. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980656/ PMC10980656]</ref>

	[[Category:Drugs]]		[[Category:Drugs]]
	[[Category:Lifespan interventions]]		[[Category:Lifespan interventions]]
	[[Category:Main list]]		[[Category:Main list]]

Dmitry Dzhagarov: /* Verapamil */

2024-06-28T14:16:00Z

Verapamil

← Older revision		Revision as of 14:16, 28 June 2024
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	Verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity.<ref>Liu, W., Lin, H., Mao, Z., Zhang, L., Bao, K., Jiang, B., ... & Li, J. (2020). Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy. Aging (Albany NY), 12(6), 5300. PMID: 32208362 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138547 PMC7138547] DOI: 10.18632/aging.102951</ref>		Verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity.<ref>Liu, W., Lin, H., Mao, Z., Zhang, L., Bao, K., Jiang, B., ... & Li, J. (2020). Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy. Aging (Albany NY), 12(6), 5300. PMID: 32208362 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138547 PMC7138547] DOI: 10.18632/aging.102951</ref>

			== Fasudil ==
			The small molecule fasudil, formerly known as HA1077 or AT‐877, is the ROCK inhibitor that has been used in Japan and China since 1995 for the treatment of vasospasms following subarachnoid haemorrhage, as well as to prevent the loss of intelligence and memory observed in stroke patients and the elderly.<ref>Suzuki, Y., Shibuya, M., Satoh, S. I., Sugimoto, Y., & Takakura, K. (2007). A postmarketing surveillance study of fasudil treatment after aneurysmal subarachnoid hemorrhage. Surgical neurology, 68(2), 126-131. PMID: 17586012 DOI: 10.1016/j.surneu.2006.10.037</ref> Fasudil also could ameliorate impairments in skeletal muscle blood flow observed in older adults<ref>Darvish, S., Coppock, M. E., & Murray, K. O. (2022). Age-related impairments in ATP release by red blood cells as an important contributor to declines in skeletal muscle blood flow in older adults. The Journal of physiology, 600(16), 3643. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378623/ PMC9378623]</ref> It is marketed under the name ERIL®. It was initially characterized as a calcium antagonist, different from previously known calcium channel blockers such as verapamil, diltiazem and nicardipine in that it could prevent arterial contraction in conditions where other calcium channel blockers had failed.<ref>Asano, T. O., Ikegaki, I. C., Satoh, S.,et al., & Hidaka, H. (1987). Mechanism of action of a novel antivasospasm drug, HA1077. Journal of Pharmacology and Experimental Therapeutics, 241(3), 1033-1040. PMID 3598899</ref>

			Despite its successful introduction into clinical practice in Japan and China for almost 30 years, the use of fasudil in other countries faces certain limitations. Although fasudil inhibits both ROCK isoforms (ROCK1 and ROCK2) more potently than other kinases, some of its side effects, including hypotension, skin reactions and reversible renal dysfunction, are major barriers to its widespread use.<ref>Wolff, A. W., Peine, J., Höfler, J., Zurek, G., Hemker, C., & Lingor, P. (2024). SAFE-ROCK: A Phase I Trial of an Oral Application of the ROCK Inhibitor Fasudil to Assess Bioavailability, Safety, and Tolerability in Healthy Participants. CNS drugs, 38(4), 291-302. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10980656/ PMC10980656]</ref><ref></ref>

	[[Category:Drugs]]		[[Category:Drugs]]
	[[Category:Lifespan interventions]]		[[Category:Lifespan interventions]]
	[[Category:Main list]]		[[Category:Main list]]