The antiarrhythmic and cardiovascular properties of 1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride, UM-424.
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.
D000319:Adrenergic beta-Antagonists; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002415:Cats; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D000644:Quaternary Ammonium Compounds; C011588:UM-424; D010042:Ouabain; D007545:Isoproterenol