EVALUATION OF NEGATIVE INOTROPIC EFFECTS OF A ISOQUINOLINE ALKALOID DERIVATIVE, 1-(4-DIMETHYLAMYPHENYL)-6,7-DIMETHOXY-1,2,3,4-TETRAHYDROISOQUINOLINE.

Abstract

This study evaluated the mechanism of the negative inotropic effect of an isoquinoline alkaloid derivative, 1-(4-dimethylamyphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (F-24) using electrically stimulated rat left ventricular papillary muscle. F-24 produced a pronounced negative inotropic effect in a dose-dependent manner. This effect of F-24 was depended on the Ca²⁺ concentration in the bathing media and markedly reduced in the presence of nifedipine. Moreover, the negative inotropic effect of F-24 was decreased in the presence of lidocaine and in external media with high KCl (26 mM). Furthermore, F-24 significantly decreased contraction induced by low Na⁺ solution and ouabain, as well as, markedly inhibited post-rest potentiation of contraction. We conclude that the negative inotropic effect of F-24 may be mediated by multiple mechanisms involving either direct or indirect modulation of Ca²⁺ handling in cardiomyocytes resulting in a reduction in the amount of Ca²⁺ released from the SR and suppression of the contraction force.