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Pharmacological actions of the selective and non‐selective β‐adrenoceptor antagonists celiprolol, bisoprolol and propranolol on human bronchi
Author(s) -
Hauck R.W.,
Schulz Ch.,
Emslander H.P.,
Böhm M.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17098.x
Subject(s) - celiprolol , bisoprolol , propranolol , pharmacology , radioligand , chemistry , isoprenaline , endocrinology , medicine , receptor , heart rate , stimulation , heart failure , blood pressure
1 The pharmacological actions of the β‐adrenoceptor antagonists, celiprolol, bisoprolol and propranolol were investigated in human lung tissue by radioligand binding experiments as well as in human isolated bronchi by functional experiments in organ baths. 2 Data from lung tissue were compared to those obtained from myocardial membranes. 3 Lung tissue was obtained from 10 patients having undergone lung resection for bronchial carcinoma and myocardial tissue from a patient who had received a heart transplantation. 4 In radioligand binding experiments, celiprolol exhibited a high affinity binding to β 1 ,‐adrenoceptors in heart and a low affinity binding to β 2 ‐adrenoceptors in lung tissue. The selectivity obtained for the β 1 ‐adrenoceptor was calculated to a factor of eleven. 5 Compared to bisoprolol and propranolol, celiprolol elicited the lowest affinity for the β‐adrenoceptor, as judged from the K 1 ‐values. 6 In the absence and presence of the guanine nucleotide Gpp(NH)p celiprolol did not affect receptor binding. 7 In functional experiments on intact bronchi, celiprolol, bisoprolol and propranolol failed to produce relaxation (± forskolin) or a significant difference in efficacy in antagonizing the relaxant effects of isoprenaline. However, a rank order of potencies was revealed (propranolol: bisoprolol.celiprolol = 46: 12:1). 8 Plasma concentrations for celiprolol and bisoprolol usually achieved in vivo were below the IC 50 value obtained in vitro . In contrast, for propranolol, plasma concentrations were nearly identical with the IC 50 value. 9 It is concluded that celiprolol is a selective β 1 ‐adrenoceptor antagonist on human heart and has no agonistic properties on intact human bronchi. Compounds such as celiprolol and bisoprolol may in comparison to propranolol, possess reasonable therapeutic advantages in the treatment of patients with obstructive lung disease due to their low affinity for β 2 ‐adrenoceptors.