Antiarrhythmic Effect of 1-(3ˊ-Bromophenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline Hydrochloride
Abstract
During the study, the inotropic and antiarrhythmic properties of the alkaloid 1-(3ˊ-Bromophenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (F-25) were investigated. The alkaloid F-25 was shown to exert a negative inotropic effect on the contractile force of rat cardiac papillary muscle, decreasing myocardial contractility by 87.6±4.2% at a concentration of 100 μM compared to the control. To assess the involvement of voltage-gated Na+ channels in providing the negative inotropic effect of the alkaloid F-25, experiments were conducted using lidocaine, a specific blocker of this channel. When the effect of F-25 alkaloid (100 μM) was tested in the existence of lidocaine (IC50=15.4 μM), the amplitude of papillary muscle contraction force was 32.8±3.9%, respectively. The influence of the alkaloid F-25 on Na⁺/Ca²⁺ exchange was examined using NiCl₂, a non-specific blocker of this exchanger. The negative inotropic effect of the alkaloid F-25 (100 μM) on papillary muscle contraction activity in the presence of a 10 mM concentration of NiCl2 in the incubation medium was 42.3±4.2%. The negative inotropic effect of the alkaloid F-25 is exerted mainly by modulating the function of Na+ channels and, in part, the Na+/Ca2+ exchange. The impact of the alkaloid F-25 was also evaluated using an aconitine-induced arrhythmia model, revealing that the compound exhibits strong antiarrhythmic properties