M. Okuhira et al., BETA-BLOCKING ACTION OF BOPINDOLOL, A NEW BETA-BLOCKER, AND ITS ACTIVE METABOLITES IN OPEN-CHEST DOGS, Archives internationales de pharmacodynamie et de therapie, 323, 1993, pp. 5-15
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.