THE CARDIOVASCULAR PHARMACOLOGY OF BUNOLOL, A NEW BETA ADRENERGIC BLOCKING AGENT

¹ Warner-Lambert Research Institute, Morris Plains, New Jersey

Bunolol, dl-5-[3-(tert.-butylamino)-2-hydmxypropoxy]-3,4-dihydro-1-(2H)-naphthalenone hydrochloride, was approximately 3 times as potent as propranolol by i.v. administration in anesthetized dogs in antagonizing the cardiovascular actions of isoproterenol and the response to cardioaccelerans nerve stimulation. However, when p.o. doses were given to unanesthetized dogs with subsequent induction of anesthesia, bunolol was estimated to be approximately 20 times as potent as propranolol. The beta adrenergic blocking activity of bunolol appeared to be competitive, and the activity was largely restricted to the l-isomer. Bunolol demonstrated high specificity and a persistent action and was equally effective at beta receptors of the myocardium and the smooth muscle of the coronary arteries and femoral vasculature. Heart rate and contractile force of anesthetized dogs with intact sympathetic nerves declined as a consequence of beta adrenergic blockade; however, rate and force were not significantly reduced in reserpine-treated animals. Bunolol had no beta sympathomimetic activity. At large doses, bunolol caused direct myocardial depression in reserpine-treated dogs and hypotension in unanesthetized dogs.