BETA-BLOCKING ACTION OF BOPINDOLOL, A NEW BETA-BLOCKER, AND ITS ACTIVE METABOLITES IN OPEN-CHEST DOGS

The beta-blocking activity of bopindolol, a new nonselective beta-bloc ker, and of its active metabolites (18-502 and 20-785) was compared wi th that of propranolol and atenolol in anesthetized open chest dogs. N o remarkable changes in basal cardio-hemodynamic parameters were obser ved in all groups, except for dp/dt(max) which was decreased in the bo pindolol-, propranolol- and atenolol-treated groups. All beta-blockers used inhibited the isoproterenol (0.1 mug/kg, i.v.)-induced tachycard ia and the increase in myocardial oxygen consumption dose-dependently. The active metabolite 18-502 was the most potent; it was 19 times as potent as propranolol with respect to the antitachycardic action and 3 4 times as potent as propranolol in inhibiting the increase in oxygen consumption induced by isoproterenol (0.1 mug/kg). The potency of bopi ndolol was nearly equal to that of propranolol, while the potency of a tenolol and the metabolite 20-785 was weaker than that of propranolol. As 18-502 was found as a metabolite also in man, it is suggested that 18-502 is a more important active metabolite of bopindolol than 20-78 5 in in vivo conditions, though the metabolite 20-785 is also a potent beta-blocker.