Antiarrhythmic and electrophysiologic effects of MDL 11,939, a novel class III antiarrhythmic agent in anesthetized dogs.
MDL 11,939 (alpha-phenyl-1-[2-phenylethyl]-4-piperidine-methanol) is a new class III antiarrhythmic agent that was evaluated for antiarrhythmic activity in anesthetized dogs. Intravenous (i.v.) administration of MDL 11,939 (1, 3, and 10 mg/kg) increased left ventricular effective refractory periods. Q-T interval, and Q-Tc in a dose-related way. The effects of MDL 11,939 on ventricular refractoriness were similar to those observed with administration of identical doses of d-sotalol, with the exception that those produced by MDL 11,939 lasted longer. Intraduodenal administration of 10 mg/kg MDL 11,939 also increased left ventricular effective refractory period (LV ERP). The increase in left ventricular refractoriness produced by MDL 11,939 occurred without a significant increase in QRS duration. MDL 11,939 (10 mg/kg i.v.) also protected against induction of ventricular tachycardia (VT) and ventricular fibrillation (VF) induced with programmed electrical stimulation (PES) in anesthetized dogs with chronic 4- to 7-day myocardial infarctions. In comparison, antiarrhythmic effects of bretylium (10 mg/kg i.v.) against PES-induced ventricular arrhythmias were dependent on additional administration of propranolol (0.1 mg/kg i.v.), whereas propranolol alone (0.1 mg/kg i.v.) was ineffective. The results observed with MDL 11,939 are consistent with its in vitro class III antiarrhythmic action and suggest utility for this agent in treatment of VT and VF.
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001949:Bretylium Compounds / Q000627:therapeutic use; D004285:Dogs; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011433:Propranolol / Q000627:therapeutic use; D013610:Tachycardia / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D001949:Bretylium Compounds; D010880:Piperidines; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol; D011433:Propranolol; C045166:bretylium