Relationships between ventricular arrhythmias and plasma concentrations of ME3202 (CM7857) in dogs

Two-stage coronary ligation-, digitalis-, and epinephrine (EPI)-induced ventricular arrhythmias were used to establish minimum effective plasma concentrations of ME3202 in dogs. 2-(2-Diisopropylaminoethyl)-4-methyl-2-(2-pyridyl) pentanamide (ME3202) showed antiarrhythmic effects against arrhythmias in all models. The minimum effective plasma concentrations for arrhythmias induced by 24-h coronary ligation, 48-h coronary ligation, digitalis, and EPI were 4.8 +/- 1.0 [after 5 mg/kg intravenously (i.v.)], 5.3 +/- 1.3 (after 5 mg/kg i.v.), 4.1 +/- 1.1 (after 4 mg/kg i.v.), and 2.5 +/- 0.8 (after 5 mg/kg i.v.) micrograms/ml, respectively (mean +/- SD, n = 6 or 7). The minimum effective concentration for EPI-induced arrhythmias was significantly lower than those for the other types of arrhythmias. This profile is similar to those of propafenone and nicainoprol, and since ME3202 had no deleterious effects on blood pressure (BP) or sinus node rate, it is expected to be clinically useful.