Comparative electrophysiologic profiles of calcium antagonists with particular reference to bepridil

Abstract

The calcium antagonist bepridil hydrochloride differs pharmacologically from the conventional agents that block the myocardial slow channel. Its clinical electrophysiologic effects are poorly defined. The effects of 2 mg/kg + 1 mg/kg of intravenously administered bepridil in 10 patients were compared with those of 3 mg/kg + 1 mg/kg in 9 patients undergoing electrophysiologic evaluation of clinical symptoms. The overall effects of the 2 regimens did not differ significantly. The drug reduced the heart rate slightly; it had no effect on the PR interval but significantly lengthened the AH interval by 2 to 10%, HV by 2 to 12% and QTc by 5 to 8%. The most striking effect was the prolongation of the functional (up to 17%, p less than 0.001) and the effective (up to 13%, p less than 0.001) refractory periods of the atrioventricular node with a lengthening of the Wenckebach cycle (up to 17%, p less than 0.001). In contrast to the action of verapamil, bepridil significantly prolonged the ventricular (4 to 7%, p less than 0.01 to p less than 0.001) and the atrial (12 to 19%, p less than 0.05 to p less than 0.001) effective refractory periods. The data indicate that bepridil hydrochloride has a wide spectrum of electrophysiologic activity in man consistent with inhibitory actions on myocardial slow and fast channels and a significant lengthening of cardiac repolarization. These overall effects suggest that the antiarrhythmic profile of the drug is likely to be wider than those of conventional calcium antagonists.