d-Sotalol: a new potent class III anti-arrhythmic agent.
We have compared the effect of a new drug d-sotalol which has minimal beta-blocking action with the parent (beta-blocking) compound dl-sotalol on monophasic action potential (MAP) duration in open-chested dogs. In seven experiments d-sotalol was administered in intravenous bolus doses of 1.5, 3 and 6 mg/kg given at 10 min intervals. In a further seven experiments dl-sotalol was administered using the same dosage regimen. The animals were anaesthetized with chloralose and urethane. Atrioventricular block was created by injection of the bundle of His with 0.1 ml of 40% formalin in order to ensure capture by ventricular pacing. After prior beta-blockade with propranolol (0.25 mg/kg), simultaneous epicardial and endocardial MAP were recorded at paced heart rates of 100 and 150 beats/min after each bolus injection. d-Sotalol and dl-sotalol showed similar prolongation of MAP duration (measured at 90% repolarization) in both endocardial and epicardial recording at both paced heart rates. These results show that the dextro-isomer of sotalol possesses similar class III action to the parent compound and that this action is homogeneous with respect to left ventricular endocardium and epicardium at heart rates of 100 beats/min and 150 beats/min over a wide dose range. d-Sotalol may be a useful anti-arrhythmic agent in man.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D004285:Dogs; D004699:Endocardium / Q000502:physiology; D005260:Female; D006327:Heart Block / Q000503:physiopathology; D006339:Heart Rate; D008297:Male; D010496:Pericardium / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D011433:Propranolol; D013015:Sotalol