Cardiovascular effects of dl-1-(2-acetyl-4-butyramido-phenoxy)-2-hydroxy-3-isopropylaminopropane (M & B 17,803A), a new cardioselective beta adrenoreceptor blocking agent.

Abstract

The direct and beta adrenergic blocking effect of M& B 17, 803A was investigated in the isolated supported dog heart preparation (ISHP) in the presence of a constant coronary blood flow. Administration of graded doses of norepinephrine into the coronary arteries produced a dose-dependent increase in the heart rate, myocardial contractile force, left ventricular systolic pressure and coronary artery perfusion pressure. The myocardial oxygen consumption was increased significantly (p<0.05) by each dose of norepinephrine. Pretreatment of the ISHP with 0.3mg/Kg of M & B 17, 803A produced a generalized myocardial depression and an increase in coronary artery perfusion pressure, whereas the smaller dose (0.15mg/Kg) of the blocking agent was without any effect. Both the doses of M & B 17, 803A produced a competitive blockade of the effect of norepinephrine on the myocardial hemodynamics and oxygen consumption. M&B 17, 803A thus appears to be a potent agent that blocks the beta receptors, and has a significant myocardial depressant activity.