Cardiac actions in the dog of a new antagonist of adrenergic excitation which does not produce competitive blockade of adrenoceptors

Abstract

1. The cardiac actions of amiodarone, a benzofuran derivative used in the treatment of angina pectoris, have been compared with those of (+/-)-propranolol in anaesthetized dogs.2. After three successive intravenous injections of propranolol, 0.5 mg/kg, had reduced the heart rate by 25%, a fourth dose had no further negative chronotropic action, but amiodarone, 10 mg/kg intravenously, at this point reduced the heart rate by 23%.3. Amiodarone, 10 mg/kg intravenously, reduced, but did not abolish, cardiac responses to isoprenaline, 2 mug/kg intravenously. Subsequent successive injections of 10 mg/kg of amiodarone did not further block the responses to isoprenaline, but propranolol, 1 mg/kg intravenously, abolished them.4. Amiodarone reduced cardiac chronotropic and inotropic responses to glucagon, which were not affected by propranolol.5. Cardiac output was increased 5 min after amiodarone, 10 mg/kg intravenously, but at 10 min and thereafter it did not differ from control values. Propranolol, 1 mg/kg intravenously, reduced cardiac output by 17% at 5 min, and by 30% after 30 min.6. From this and other evidence which is discussed, it is concluded that the cardiac actions of amiodarone are not produced by competitive blockade of beta-adrenoceptors.