Antiarrhythmic evaluation of verapamil, nifedipine, perhexiline and skf 525-A in four canine models of cardiac arrhythmias.

Verapamil, nifedipine, perhexiline and SKF 525-A (2-diethylaminoethyl-2,2-diphenylvalerate . HCL) were evaluated for cardiac antiarrhythmic activity by assessing their effectiveness in increasing left ventricular fibrillation threshold (FT) and antagonizing ouabain-induced arrhythmias (OA), 24 h post infarction arrhythmias (CLA) and aconitine-induced atrial arrhythmias. Calcium antagonistic doses (ID50) of each agent were approximated by intravenous titration of the amount of drug required to reduce the left ventricular contractile force by 50% in dogs pretreated with hexamethonium (10 mg/kg) to block autonomic reflexes. ID50 doses of calcium antagonists were found not to be universally effective in any single arrhythmia model while causing significant changes in heart rate, blood pressure and frequently producing death or convulsion. It is suggested that local anesthetic or 'class 1' action probably accounts for the antiarrhythmic effectiveness of SKF 525-A (7-20 mg/kg i.v.) in all four arrhythmia models and for perhexiline-induced increased FT and antagonism of CLA (15-20 mg/kg). Antiarrhythmic effectiveness of verapamil against OA may be due to calcium antagonism action.