ANTIARRHYTHMIC ACTION OF THE NEW CALCIUM-ANTAGONIST ANOETHYL-N-4'-METHOXYBENZYL)-ETHYLAMINO]PIPERIDINE DIHYDROCHLORIDE

Arrhythmias induced by coronary artery ligation in cats, by CaCl2 and epinephrine in rats, and by ouabain in guinea-pigs were used as experi mental models for studing the effects of a new calcium antagonist AR-1 yanoethl-N-4'-methoxybenzyl)-ethylamino]pireridine calcium channel bl ocker and calmodulin antagonist) on ventricular arrhythmias. Coronary ligation caused 90 % lethality (ventricular fibrillation) within 12.5 min in untreated control cats, which was prevented by administration o f AR-1 (4 mg/kg body weight (b.w.) before or after arrhythmia inductio n. Pretreatment with AR-1 afforded protection in a dose-related fashio n. A dose of 1.5 mg/kg b.w. increased survival to 45 % and all cats do sed with 3 to 5 mg/kg b.w. survived. CaCl2 (180 mg/kg b.w. i.v.) induc ed ventricular fibrillation and 100 % lethality. These effects were co mpletely prevented by an anti-arrhythmic dose of AR-1 (3 mg/kg b.w). E pinephrine-induced ventricular arrhythmias were also prevented by the same dose of AR-1. AR-1 (5 mg/kg b.w. did not prevent ouabian (0,5 mg/ kg b.w.)-induced arrhythmias that caused death within 17 +/- 3.7 min, but displayed protective effects during 67 +/- 7.1 min. The results fr om these animal studies, in conjunction with previously studies demons trating coronarodilatory and anti-platelet efficacy of this compound, collectively suggest that AR-I has a potential to became. a useful ant ianginal and antiarrhythmic therapeutic agent.