The antagonist and partial beta agonist properties of celiprolol in isolated rat cardiac tissue.
Celiprolol was evaluated for its antagonist and partial beta agonist effects in rat spontaneously beating right atria and in electrically stimulated left ventricular strips. Celiprolol, like propranolol, produced a parallel concentration-related rightward shift of the isoproterenol (ISO) (beta agonist) concentration-response curve without decreasing the maximum response in rat right atria. The pA2 values for celiprolol and propranolol were 7.02 +/- 0.30 and 8.45 +/- 0.29, respectively. Unlike propranolol, however, celiprolol increased the resting spontaneous rate at concentrations 3 X 10(-7) to 10(-4)M. ISO alone produced a concentration-related increase in heart rate of rat right atria (maximum 149 +/- 15 bpm at 3 X 10(-7)M). Whereas, celiprolol increased atrial rate a maximum of 49 +/- 5 bpm at 10(-6)M. ISO produced a concentration-related increase in the developed tension of rat right ventricular strips (maximum 79 +/- 4% at 10(-6)M. Celiprolol, by contrast, had no effect on developed tension in concentrations up to 10(-3)M. In separate experiments, celiprolol alone increased right atrial rate a maximum of 40 +/- 6 bpm at 10(-5)M. Pretreatment with propranolol (10(-6)M) completely blocked the increase in rate. It is concluded that celiprolol is a potent and competitive beta antagonist and a partial agonist with approximately 33% of the efficacy (comparing maximum stimulating concentrations) and 0.01 the potency of ISO in rat right atria (at ED50 concentrations). Celiprolol, however, unlike ISO, has no inotropic effect in rat ventricular strips suggesting possible differences in their agonist properties.
Smith
R D
RD
Cobuzzi
A
A
Wolf
P S
PS
Pruss
T P
TP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017272:Celiprolol; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011433:Propranolol; D017272:Celiprolol; D007545:Isoproterenol