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-blocker, and of its active metabolites (18-502 and 20-785) was compared with that of propranolol and atenolol in anesthetized open chest dogs. No remarkable changes in basal cardio-hemodynamic parameters were observed in all groups, except for dp/dtmax which was decreased in the bopindolol-, propranolol-and atenolol-treated groups. All beta-blockers used inhibited the isoproterenol (0.1 microgram/kg, i.v.)-induced tachycardia 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 34 times as potent as propranolol in inhibiting the increase in oxygen consumption induced by isoproterenol (0.1 microgram/kg). The potency of bopindolol was nearly equal to that of propranolol, while the potency of atenolol 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 20-785 in in vivo conditions, though the metabolite 20-785 is also a potent beta-blocker.
Okuhira
M
M
Department of Pharmacology, Niigata University School of Medicine, Japan.
Nakazawa
M
M
Kameda
H
H
Hara
K
K
Kawada
T
T
Imai
S
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; C038186:4-(2-hydroxy-3-tert-butylaminopropoxy)-2-methylindole; C061293:4-(3-tert-butylamino-2-hydroxypropoxy)-2-carboxyindole; D010869:Pindolol; C036007:bopindolol; D007545:Isoproterenol