Synthesis and positive inotropic effects of 1-acyl-5,6-diethoxy-2-methylthiobenzimidazoles

A series of 1-acyl-5,6-diethoxy-2-methylthiobenzimidazoles was synthesized and evaluated for inotropic activity. The compounds caused a concentration- dependent positive inotropic effect in isolated guinea-pig papillary muscle s. According to the estimated ED50 value, the efficacy of methyl (1) and is onicotinoyl derivatives (6) was similar to that of milrinone. Carbachol mar kedly reduced the increase of contraction force of compounds 1, 2, 5 and 9. The inotropic effect of compounds 6 and 9 does not seem to be mediated by the direct stimulation of beta-adrenergic receptors. At that lime the P-ago nistic properties of the compounds 1 and 2 might be partially involved in t he positive inotropic action of these agents. All tested derivatives, as we ll as milrinone, increased the amplitude of the late component P-2 Of the b iphasic contraction in guinea-pig papillary muscles. These results indicate that benzimidazole derivatives exert their inotropic effect by increasing Ca influx via slow calcium channel into myocardial cells.