EFFECT OF o-2-HYDROXY-3-(tert.-BUTYLAMINO) PROPOXYBENZONITRILE HCl (KO 1366) ON BETA ADRENERGIC RECEPTORS IN THE CARDIOVASCULAR SYSTEM

¹ Baker Medical Research Institute, Melbourne, Australia

The beta adrenergic blocking activity of o-2-hydroxy-3-(tert.-butylamino)propoxybenzonitrile HC1 (KO 1366) was determined in anesthetized dogs and compared with that of propranolol and ICI 50,172. KO 1366 inhibited the positive inotropic and chronotropic and the vasodilator response to isoproterenol and abolished the cardiac effects of stellate ganglion stimulation. The beta blocking potency of KO 1366 exceeded that found for either propranolol or ICI 50,172, and the blockade was specific for beta adrenergic receptors. Effective beta blocking doses of KO 1366 did not have any intrinsic negative and instead had a small positive inotropic effect on cardiac contraction. KO 1366 provided protection against halothane-epinephrine- but not against ouabain-induced arrhythmias. In contrast to propranolol, KO 1366 reduces peripheral vascular resistance. KO 1366 is, therefore, a potent beta- adrenergic antagonist which lowers peripheral vascular resistance.