| Abstract: | The electrophysiological and antiarrhythmic effects of a structurally novel compound, SD-3212, were evaluated in comparison with its enantiomer (SD-3211). In isolated guinea pig ventricular muscles, SD-3212 reduced the maximum upstroke velocity and the plateau phase of action potential in a concentration-dependent manner, while SD-3211 significantly affected only action potential duration. SD-3212 had oral prophylactic effects against both ouabain-induced (in guinea pigs) and chloroform-induced (in rats) arrhythmas, whereas SD-3211 and verapamil were effective only on the former arrhythmia model and mexiletine was effective only on the latter. These results suggest that there is an enantiospecific interaction with cardiac Na+ and Ca++ channels, and that the dual inhibitory action of SD-3212 on these channels may contribute to its antiarrhythmic properties. |
