Cardiac actions in the dog of a new antagonist of adrenergic excitation which does not produce competitive blockade of adrenoceptors.
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.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005260:Female; D005934:Glucagon / Q000037:antagonists & inhibitors; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001572:Benzofurans; D005934:Glucagon; D011433:Propranolol; D007545:Isoproterenol; D004837:Epinephrine