Antitachycardiac Effect of OPC-8212, a Novel Cardiotonic Agent, on Tachycardiac Responses of Guinea Pig Isolated Right Atria to Isoproterenol and Histamine

Abstract

In isolated right atria of guinea pigs, OPC-8212 produced a concentration-dependent decrease in spontaneous beating rate that had previously been elevated by isoproterenol or histamine in the presence of nadolol. OPC-8212 scarcely affected the baseline rate, however, OPC-8212 depressed the maximum increase in right atrial rate induced by isoproterenol or histamine in the presence of nadolol. These effects of OPC-8212 were discernible from the effects of its solvent sulfolane. We propose the term "antitachycardiac" to describe such effects of OPC-8212 to distinguish it from those of bradycardic agents. When the concentration-response curves of isoproterenol or histamine for positive chronotropy were normalized, these curves were shifted in a parallel way to the left with OPC-8212, indicating that OPC-8212 retains activity as a cyclic AMP phosphodiesterase inhibitor. The virtual absence of the chronotropic effect of OPC-8212 on the baseline rate and the antitachycardiac effect are discussed in terms of the opposing effects in increasing the inward calcium current on one hand and in decreasing the outward potassium and the inward current activated by hyperpolarization on the other.