Antiarrhythmic effects of DPI 201-106.

The cardiotonic agent DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl-2- hydroxypropyl]-1H-indole-2-carbonitrile) which modifies the sarcolemmal Na+ channel gating system and has electrophysiological properties of class III antiarrhythmics was investigated for local anaesthetic and antiarrhythmic activity. The compound action potential amplitude of cat cervical vagus nerves in vitro was decreased by DPI 201-106 in a concentration-dependent manner, the IC50 being 1.82 X 10(-5) M. This was paralleled by a slowing in conduction velocity and demonstrates local anaesthetic effects. Ventricular fibrillation which occurs in response to coronary artery reperfusion in rats was prevented by intravenous infusions of 0.3 mg kg-1 min-1 of DPI 201-106. The arrhythmogenic intravenous doses of aconitine in rats were increased following pretreatment with DPI 201-106 in a dose-dependent manner. DPI 201-106 did not protect against ouabain-induced arrhythmias in guinea-pigs. The results demonstrate that DPI 201-106 has local anaesthetic effects and is a potential antiarrhythmic.