A COMPARATIVE STUDY OF THE BETA ADRENERGIC BLOCKING ACTIVITIES OF PROPRANOLOL AND INPEA

¹ Smith Kline & French Laboratories, Philadelphia, Pennsylvania

Beta receptor blockade after propranolol and N-isopropyl-p-nitrophenylethanolamine (INPEA) was studied in both nonanesthetized and anesthetized dogs. In the conscious dog, inhibition of isoproterenol-induced tachycardia was dose-related after propranolol (0.2-3.2 mg/kg p.o.) and INPEA (3.2-38.4 mg/kg p.o.) treatment. Propranolol had no effect on resting heart rate whereas INPEA increased it at each dose level. In the anesthetized dog, propranolol (10-1250 µg/ kg i.v.) produced dose-related inhibition of the cardiac and vascular effects of a standard dose of isoproterenol and produced small reductions in resting myocardial contractile force. INPEA (0.5-12.5 mg/kg i.v.) produced similar inhibition of the agonist challenge and at low doses increased resting contractile force. The administration of 50 and 1250 µg/kg of propranolol produced significant reductions in mean blood pressure, coronary and aortic blood flow, left ventricular work and heart rate. Significant increases in coronary vascular resistance and mean left atrial pressure were also observed after each of these doses of propranolol, but total peripheral resistance was elevated significantly only after 50 µg/kg. Stroke volume remained unchanged after propranolol treatment. After doses of 2.5 and 12.5 mg/kg of INPEA, mean blood pressure and coronary blood flow were significantly lowered, while left ventricular work was reduced to a significant level only with the latter dose. In contrast to propranolol, INPEA slightly increased stroke volume and lowered total peripheral resistance, but had no effect on coronary resistance, aortic blood flow or mean left atrial pressure.