Asocainol, a new antiarrhythmic drug with natrium- and calcium-antagonistic effects on ventricular myocardium.
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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001392:Azocines / Q000494:pharmacology*; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008274:Magnesium / Q000037:antagonists & inhibitors; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001392:Azocines; D002121:Calcium Channel Blockers; D007473:Ion Channels; D001464:Barium; D008274:Magnesium; C042287:asocainol