Antiarrhythmic effect of KB-944, a new calcium antagonist. A comparison with verapamil and diltiazem

Effects of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944), a new chemical class of Ca-antagonist, on three types of experimentally induced arrhythmias were evaluated and compared with those of verapamil and diltiazem. KB-944 at 0.02 to 0.1 mg/kg (i.v.) effectively reversed ventricular arrhythmias induced by a continuous infusion of ouabain into guinea-pigs, and its effect was 2 times more potent than that of diltiazem and 5 times less potent than that of verapamil. Epinephrine(adrenaline)-induced arrhythmias in guinea-pigs were prevented by an i.v. injection of KB-944 in doses of 0.025 to 0.2 mg/kg. KB-944 was approximately equipotent with diltiazem and 2 times less potent than verapamil. CaCl2-induced arrhythmias in rats were inhibited by KB-944 with rather high doses (ED50 2.6 mg/kg i.v.). The antiarrhythmic effect of KB-944 was 1.7 times less potent than that of diltiazem and 5 times less potent than that of verapamil. KB-944 was found to possess antiarrhythmic activities in animals qualitatively similar to those of verapamil and diltiazem.