Encainide is a class IC agent possessing a broad spectrum of antiarrhythmic actions in a variety of animal models. It increases the
ventricular fibrillation threshold of the perfused rabbit heart and in situ dog myocardium.
Encainide suppresses
atrial fibrillation resulting from topical application of
aconitine in the anesthetized dog and
ventricular fibrillation induced by
chloroform asphyxiation in the mouse. In these latter 2 models,
encainide is approximately 7 to 11 and 16 to 18 times more potent, respectively, on a milligram basis than
quinidine. In anesthetized dogs
encainide converts
ouabain-induced
tachyarrhythmias to normal sinus rhythm at a mean intravenous dose of 0.67 mg/kg. Single doses of 0.5 mg/kg intravenously or 1 mg/kg orally significantly reduced ventricular ectopy in conscious dogs 18 to 22 hours after 2-stage
ligation of the left coronary artery. At doses and plasma concentrations exceeding efficacious therapeutic levels,
encainide has no major negative inotropic effects and does not compromise cardiac function or hemodynamics. It is devoid of peripheral autonomic or mediator-evoked responses and, in particular, lacks
anticholinergic actions.
Encainide is rapidly absorbed by all routes of administration and extensively metabolized by the liver. The major metabolites, O-demethyl
encainide and 3-methoxy-O-demethyl
encainide, have been shown to have quantitatively different, but qualitatively similar, profiles of pharmacodynamic effects. Subacute and chronic administration of
encainide at doses representing 11 times an effective oral human dose have produced no distinct or consistent toxicologic findings. Carcinogenicity and mutagenicity studies were negative.(ABSTRACT TRUNCATED AT 250 WORDS)