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Beta‐1 antagonist and cardiostimulatory effects of celiprolol in anesthetized dogs
Author(s) -
Barrett John A.,
Smith Ronald D.,
Wolf Peter S.,
Pruss Thaddeus P.
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430090208
Subject(s) - celiprolol , atenolol , propranolol , antagonist , heart rate , ed50 , hemodynamics , beta (programming language) , chemistry , medicine , blood pressure , endocrinology , pharmacology , anesthesia , receptor , computer science , programming language
Celiprolol is a new cardioselective beta adrenoceptor antagonist presently undergoing worldwide clinical traits. The present study was undertaken to further evaluate the beta antagonist and hemodynamic effects of celiprolol compared to the known beta antagonists propranolol, atenolol, and dichloroisoproterenol (DCI). The results show that celiprolol up to 1 mg/kg i.v. had no significant effect on contractile force (CF), heart rate(HR) or mean, arterial pressure (AP) in normal anesthetized dogs. In these animals, however, celiprolol produced a dose‐related decreases in the beta‐1 response to isoproterenol (ISO; ED50=0.01 for CF and 0.06 mg/kg, i.v. for HR) while having a lesser effect on the AP (beta‐2) responses to ISO (ED50 =1.8 mg/kg, i.v.). Celiprolol was equipotent to propranolol and atenolol in antagonizing the beta‐1‐mediated effects of ISO while being equipotent to atenolol and 300 times less potent than propranolol in antagonizing the beta‐2‐mediated effects. In mecamylamine‐pretreated dogs, celiprolol (1 and 3 mg/kg, i.v.) produced limited but significant increases in CF (25 ± 7 and 48 ± 10%, respectively) and HR (18 ± 1 and 22 ± 2%, respectively). DCI (0.1 mg/kg, i.v.) produced a more marked increase in CF (79 ± 9%) and HR (33 ± 7%). By contrast, atenolol 3 mg/kg i.v. and propranolol 1 and 3 mg/kg i.v. significantly depressed both CF and HR. None of the treatments had consistent effects on arterial pressure or aortic flow. In mecamylamine‐and propranolol‐pretreated dogs, celiprolol 1 or 3 mg/kg i.v. still produced a significant increase in CF (31 ± 9 and 21 ± 6%, respectively) and HR (15 ± 2 and 17 ± 3%, respectively). By contrast, the cardiostimulatory effects of DCI were completely abolished by propranolol. It is concluded that celiprolol is a potent and cardioselective beta adrenoceptor antagonist with mild cardiostimulatory effects only partially attributable to beta receptor stimulation.