Partial agonist activity of celiprolol, a cardioselective beta-antagonist.
The beta-antagonistic effects of celiprolol were assessed in isolated guinea-pig preparations. The pA2 values obtained were 7.84 +/- 0.07, 7.79 +/- 0.06 and 6.45 +/- 0.11 against the positive chronotropic and inotropic effects in the atria and relaxant effects in the trachea induced by isoproterenol, respectively, indicating that celiprolol is a cardioselective beta-antagonist. Celiprolol produced slight positive chronotropic and inotropic effects in atrial preparations and a uniquely strong relaxant effect in tracheal preparations. All these effects were attenuated by pretreatment with 10(-6) M atenolol or 10(-6) M propranolol. In pithed rats, celiprolol produced pressor responses at doses lower than 0.03 mg/kg and hypotensive responses at doses higher than 0.3 mg/kg. It produced sustained increases in heart rate in all doses applied. These effects were attenuated by pretreatment with 1 mg/kg of propranolol. The pressor response might be taken to be a reflection of an increase in cardiac function mediated by cardiac beta 1-receptor stimulation, while the hypotension may be ascribed mainly to stimulation of beta 2-adrenoceptors in the vascular system. It is concluded that celiprolol exerts a uniquely strong partial agonist activity at beta 2-adrenoceptors.
Department of Pharmacology, Niigata University School of Medicine, Japan.
S
S
Ochi
M
M
Nakazawa
T
T
Kimura
Y
Y
Nakagawa
S
S
Imai
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D017272:Celiprolol; D003655:Decerebrate State; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014132:Trachea / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D017272:Celiprolol; D007545:Isoproterenol