The antiarrhythmic and cardiovascular properties of 1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride, UM-424

FJ Kniffen, S Winokur, RE Counsell and BR Lucchesi

The quarternary ammonium compound, UM-424 [1-dimethyl isopropylamino-3- (2-phenylphenoxy)-propan-2-ol chloride], was evaluated for its antiarrhythmic and hemodynamic effects. UM-424 converted ouabain- induced ventricular tachycardia in the anesthetized dog when administered in an average dose of 4.6 mg/kg i.v. Pretreatment of anesthetized dogs with UM-424, 10 mg/kg, provided complete protection against the development of premature beats and ventricular fibrillation when the left anterior descending coronary artery was occluded for 20 minutes and then released. UM-424 was effective in reversing ventricular arrhythmias in conscious animals which had been subjected to a two-stage ligation of the anterior descending coronary artery. The mean ectopic rate in a group of five dogs was 143 +/- 4.0 (S.E.M.) beats/min 24 hours after coronary ligation. Normal sinus rhythm was restored with a mean dose of 9.5 mg/kg of UM-424 and was maintained for a period in excess of 60 minutes. The ventricular fibrillation threshold was increased from a control value of 4.0 +/- 0.4 to 26.2 +/- 8.6 mA (P less than .05) 30 minutes after pretreatment with UM-424, 10 mg/kg. Inotropic and chronotropic dose-response studies to isoproterenol in the anesthetized dog demonstrated that the quarternary compound lacked beta adrenergic receptor blocking properties. UM-424, 10 mg/kg, did not produce any persistent changes in spontaneous heart rate, cardiac contractile force, left ventricular dP/ct, mean arterial blood pressure, cardiac output and mean pulmonary arterial pressure.

Volume 196, Issue 2, pp. 420-432, 02/01/1976
Copyright © 1976 by American Society for Pharmacology and Experimental Therapeutics