Asocainol, a new antiarrhythmic drug with natrium- and calcium-antagonistic effects on ventricular myocardium

Abstract

In isolated guinea pig papillary muscles, asocainol, a new antiarrhythmic drug, and its optical isomers exert a concentration-dependent negative inotropic action that is due to an inhibitory influence on the slow Ca2+ influx. However, depression of contractility is always accompanied by marked alterations of normal Na+-carried action potentials; thus, overshoot and duration decline together with Na+-dependent upstroke velocity. These observations indicate that asocainol not only inhibits Ca2+ inflow, but interferes with the fast inward Na+ current. In partially depolarized ventricular muscle, asocainol lowers Ca2+-dependent contractile force as it reduces upstroke velocity, overshoot, and duration of Ca2+-mediated action potentials. Moreover, Mg2+-induced membrane activity is suppressed by asocainol. Ba2+-induced ventricular autorhythmicity, representing a model of a slow-channel-dependent ectopic pacemaker, is abolished by asocainol. We conclude that asocainol exerts mixed Na+-, Ca2+-, and Mg2+-antagonistic effects in mammalian ventricular myocardium. Thus, asocainol keeps an intermediate position between specific Ca2+ antagonists (verapamil) and predominantly Na+-antagonistic drugs such as certain local anesthetics. On the basis of this dual inhibitory action on both transmembrane Na+ and Ca2+ conductivities, it is easily understood that asocainol is a rather efficient antiarrhythmic agent that exerts in combination the particular effects of both class-I and class-IV antiarrhythmic drugs.