Comparison of Cardiovascular Effects of a New Calcium Channel Blocker AH-1058 with Those of Verapamil Assessed in Blood-Perfused Canine Heart Preparations

Abstract

The cardiovascular effects of AH-1058, a novel calcium channel blocker, were examined in comparison with those of verapamil using canine isolated, blood-perfused papillary muscle, atrioventricular node, and sinoatrial node preparations. Intravenous administration of AH-1058 (20, 50, and 100 microg/kg) or verapamil (20, 50, and 100 microg/kg) to the blood-donor dog induced negative inotropic, dromotropic, and chronotropic effects and a coronary vasodilator action in cross-circulated isolated heart preparations, simultaneously inducing the same cardiac effects in the blood-donor dog. The order of potency of the effects of AH-1058 was ventricular contraction > coronary blood flow >> atrioventricular conduction > sinoatrial automaticity, whereas that of verapamil was coronary blood flow >> atrioventricular conduction >> sinoatrial automaticity > ventricular contraction. The cardiosuppressive effects of AH-1058, especially on ventricular contraction, were slower in onset and longer lasting than those of verapamil. These results suggest that this unique cardiovascular profile of AH-1058 may become beneficial for the treatment of certain pathologic processes, in which selective inhibition of ventricular calcium channels would be essential for drug therapy.