The Effects of Encainide and Its Major Metabolites,O -Demethyl Encainide and 3-Methoxy-O -Demethyl Encainide, on Experimental Cardiac Arrhythmias in Dogs

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Abstract
Encainide (E) is a class I antiarrhythmic agent which is metabolized in humans, with the formation in the majority of patients of O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide (MODE). These metabolites may contribute to the antiarrhythmic effect of E in humans. The effects of E, ODE and MODE were investigated on ventricular arrhythmias produced by ouabain and by coronary artery ligation. In the ouabain model, E restored sinus rhythm (SR) in 8 of 13 dogs after a mean dose of 0.81 .+-. 0.19 mg/kg (mean .+-. SEM). ODE returned SR in 5 of 10 dogs after 0.30 .+-. 0.06 mg/kg and MODE returned SR in 2 of 9 dogs after doses of 0.40 and 0.68 mg/kg, respectively. In comparison, mexiletine returned SR in 6 of 6 dogs after 3.50 .+-. 1.02 mg/kg. In conscious dogs with ventricular arrhythmias 24 h after 2-stage coronary artery ligation E restored SR in 4 of 4 dogs after 2.38 .+-. 0.50 mg/kg. ODE restored SR in 4 of 4 dogs after 0.63 .+-. 0.14 mg/kg and MODE restored SR in 4 of 4 dogs after 1.39 .+-. 0.30 mg/kg. ODE and MODE had antiarrhythmic activity which may contribute to the effects of E in patients with cardiac arrhythmias.