Antiarrhythmic effect of SUN 1165, N-(2,6-dimethylphenyl) -8-pyrrolizidineacetamide hydrochloride in experimental animal models

Abstract

Antiarrhythmic actions of SUN 1165 in four experimental arrhythmia models were compared with those of disopyramide and lidocaine. SUN 1165 showed a potent and long - lasting antiarrhythmic activity against the two-stage coronary ligation-induced arrhythmia (Harris1 method) when administered i.v. or orally to conscious dogs. Its potency was 2 to 10 times that of disopyramide. The effect of i.v. or intraduodenally administered SUN 1165 was also superior to that of disopyramide in suppressing the other ventricular arrhythmia models such as ouabain-induced arrhythmia in pentobarbital anesthetized dogs and epinephrine-induced arrhythmia in halothane anesthetized dogs. Intraduodenal antiarrhythmic doses of SUN 1165 caused no block of atrio-ventricular conduction in anesthetized open-chest dogs. SUN 1165 at an orally active dose of 10 mg/kg produced slight and short-lasting decrease in the maximum rate of rise of left ventricular pressure (dP/dt max.), which was recorded as an index of cardiac contractile activity in five filaria-free healthy conscious dogs. From these results, it is concluded that SUN 1165 is a potent Class I antiarrhythmic agent with less liability to cause block of atrio-ventricular conduction and depression of cardiac contractility.