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.