Antiarrhythmic and electrophysiological effects of GYKI-16638, a novel N-(phenoxyalkyl)- N-phenylalkylamine, in rabbits

The effect of N-[4-[2- N-methyl- N-[1-methyl-2-(2,6-dimethylphenoxy)ethylamino]-ethyl]-phenyl]-methanesulfonamide.hydrochloride (GYKI-16638; 0.03 and 0.1 mg/kg, i.v.), a novel antiarrhythmic compound, was assessed and compared to that of d-sotalol (1 and 3 mg/kg, i.v.) on arrhythmias induced by 10 min of coronary artery occlusion and 10 min of reperfusion in anaesthetized rabbits. Also, its cellular electrophysiological effects were studied in rabbit right ventricular papillary muscle preparations and in rabbit single isolated ventricular myocytes. In anaesthetized rabbits, intravenous administration of 0.03 and 0.1 mg/kg GYKI-16638 and 1 and 3 mg/kg d-sotalol significantly increased survival during reperfusion (GYKI-16638: 82% and 77%, d-sotalol: 75% and 83% vs. 18% in controls, P