ANTIARRHYTHMIC AND ELECTROPHYSIOLOGIC PROPERTIES OF UM-272, DIMETHYL QUATERNARY PROPRANOLOL, IN THE CANINE HEART

¹ The University of Michigan Medical School, Department of Pharmacology, Ann Arbor, Michigan

UM-272 [N,N-dimethyl-1-isopropylamino-3-(1-naphthyloxy)-propran-2-ol], a quaternary derivative of propranolol, was evaluated for its antifibrillatory effects in the anesthetized dog. The vulnerability to ventricular fibrillation was assessed by using trains of 60-Hz square-wave pulses of 5 mA intensity and 2 msec duration. UM-272, 5 mg/kg, raised the mean fibrillation threshold from 322 ± 20 msee to 599 ± 76 msec, an increase of 185%. After a total dose of 10 mg/kg, none of the five experimental animals developed ventricular fibrillation in response to the same test parameters. When the strength of the 60-Hz pulse was increased to 10 mA, only short bursts of ventricular tachycardia were observed. The vulnerability to ventricular fibrillation after experimental coronary artery occlusion was studied before and after UM-272. In control experiments, myocardial ischemia produced a 64% decrease in the duration of the train necessary to induce ventricular fibrillation. After UM-272, 5 mg/kg, the train duration was increased to 24% above the control value of the nonischemic myocardium. UM-272 decreased the rate of atrioventricular transmission, suppressed automaticity at idioventricular pacemaker sites and prolonged the ventricular effective refractory period. The antifibrillatory and antiarrhythmic effects of UM-272 suggest that it may be a valuable new antiarrhythmic agent in the management of arrhythmias associated with acute myocardial infarction.