I. Jumayev, P. Usmanov, S. Rustamov
Mar 28, 2020
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Journal
Biomedical and Pharmacology Journal
Abstract
In this study, mechanisms of inotropic action of some isoquinoline alkaloids 1-(4-dimethylaminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (F-24), 1-(2-chloro4,5-methylenedioxyphenyl)-2-hydroxyethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (N-14) and 1-(2-chloro-4,5-methylenedioxyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (F-14) were studied. The F-24, F-14, and N-14 alkaloids have been shown to have a negative effect on papillary muscle contraction activity, IC50 value -16,8 μM, 14,03 μM and 12 μM. Ca2+L-channel blocker nifedipine, adenylate cyclase (AC) activator–forskolin, ß-adrenoreceptor (ß-AR) blocker – propranolol, protein kinase C (PKC) activator – phorbol 12-myristate 13-acetate and SR RyR2 activator caffeine were used. Inotropic effects of F-24, F-14 and N-14 isoquinoline alkaloids on cardiomyocytes were suggested, based on results obtained in experiments carried in cardiomyocytes ß-AR → [cAMP] → PKA → [Ca2+]in ↑ cascade, PKC, RyR2 and Na+/Ca2+ modulation.