[Beta-blocking actions and the partial agonist activity of bopindolol, a new beta-adrenoceptor antagonist, and its two metabolites].
The beta-blocking effects of bopindolol, a new long-acting beta-adrenoceptor antagonist, and its two metabolites, 18-502 and 20-785, were studied in the isolated atria and trachea preparations of the guinea pig. The partial agonist activity (PAA) and the membrane stabilizing activity (MSA) were studied in the pithed rat and the right ventricular papillary muscle preparations of the guinea pig, respectively. Antagonistic effect of bopindolol against isoproterenol was 1.1-2.8 and 14.1 times more potent than propranolol in the atria and the trachea preparations, respectively, while those of 18-502 were 34.7-38.0 (in atria) and 29.0 (in trachea) times more potent than propranolol. beta-Blocking potencies of 20-785 were 50% (in atria) and 10% (in trachea) of those of propranolol. Bopindolol, 18-502 and 20-785 increased the heart rate of the pithed rat dose-dependently. The effects were inhibited by pretreatment of the preparation with propranolol. The onset of action of bopindolol was slower and the duration, longer than those of its two metabolites. Bopindolol and 18-502 were more potent membrane stabilizers than propranolol, while 20-785 produced only a minimal stabilizing effect. These results indicate that not only bopindolol, but also the metabolites of bopindolol, 18-502 and 20-785 are potent beta-blocking agents with PAA. It is presumed that the long duration of action of bopindolol is due to the potent activities of its metabolites 18-502 and 20-785.
Chin
W P
WP
Department of Pharmacology, Niigata University School of Medicine, Japan.
Sun
H T
HT
Kawada
T
T
Imai
S
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013268:Stimulation, Chemical
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