Effects of MD770207 (carocainide) on experimental ventricular arrhythmias

Administered by intravenous or oral route, carocainide, MD770207, abolished experimental ventricular arrhythmias in anaesthetized and conscious dogs. Slow rate intravenous infusion (0.5 mg/kg/min) studies in conscious coronary ligated dogs demonstrated a good arrhythmia conversion as well as a wide margin of safety; mean conversion to 95% of normal sinus rhythm was achieved at 10.5 +/- 2.1 mg/kg while first signs of reversible neuro and cardio-toxicity occurred at 37.8 +/- 8 mg/kg. The reference agents disopyramide and lidocaine showed less favourable safety margin. Carocainide reduced epicardial ST-segment elevation produced by short coronary artery occlusion and prevented the occurrence of ventricular fibrillation resulting from reperfusion after acute coronary artery ligation. At antiarrhythmic dose levels there were no undesirable effects noted on cardiovascular function. Given intravenously the compound increased the ventricular fibrillation threshold in spontaneously hypertensive rats.