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Antiarrhythmic Plasma Concentrations of NIK-244 on Canine Ventricular Arrhythmias

Summary: Using two-stage coronary ligation-, digitalis-, and epinephrine (EPI)-induced canine ventricular arrhythmias, we examined antiarrhythmic effects of NIK-244 and determined the minimum effective plasma concentration for each arrhythmia model. NIK-244 suppressed coronary ligation- and digitalis-induced arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-h and 48-h coronary ligation and digitalis were 0.41 ± 0.10 (by 1 mg/kg i.v.), 0.70 ± 0.13 (by 1 mg/kg i.v.), and 0.21 ± 0.08 (by 0.5 mg/kg i.v.) μg/ml, respectively (mean ± SD of the mean, n = 6). The concentration for digitalis-induced arrhythmia was significantly lower than those for coronary ligation arrhythmias. NIK-244 was not effective on EPI arrhythmia, and 1 mg/kg worsened the arrhythmia to ventricular fibrillation in three of six dogs. This pharmacologic profile is similar to those of disopyramide, procainamide, and SUN 1165. Since NIK-244 had no deleterious effects on blood pressure and sinus node activity, its clinical usefulness is expected.