Calcium channel antagonistic effects of AH-1058, a novel antiarrhythmic drug, on guinea-pig myocardium

Effects of AH-1058, a novel cyproheptadine derivative with high antiarrhyth mic activity in in vivo arrhythmia models, were studied in guinea-pig myoca rdium. In coronary-perfused right ventricular tissue preparations, AH-1058 (10(-5)M) shortened the action potential duration with little effect on the resting membrane potential, maximum rate of rise and overshoot. AH-1058, 1 0(-7) M to 10(-5) M, concentration-dependently decreased the contractile fo rce. The increase in contractile force by Ca2+ was markedly inhibited by 3 x 10(-6) M AH-1058 while that by isoproterenol was only slightly affected. In isolated ventricular myocytes, AH-1058 concentration-dependently decreas ed the nicardipine sensitive transient inward current with no effect on ste ady state currents, and decreased the amplitude of the evoked Ca2+ transien t. These results suggest that AH-1058 has Ca2+ channel antagonistic effects which may contribute to its antiarrhythmic activity.