Comparative beta‐adrenoceptor blocking effects of propranolol, bisoprolol, atenolol, acebutolol and diacetolol on the human isolated bronchus.

Abstract

Cedex 06 and 2Laboratoires Lederle, 74, rue d'Arcueil, SILIC 275, 94578 Rungis Cedex, France Five P-adrenoceptor blockers, propranolol, acebutolol, diacebutolol, atenolol and bisoprolol, were tested for their antagonistic effect against isoprenaline on human isolated bronchi. The results showed (1) that only propranolol exerted a competitive antagonistic effect against isoprenaline (pA2 = 9.40 ± 0.22, n = 7) whereas the other drugs did not, and (2) that, in the presence of P-adrenoceptor blockers in the plasma concentrations reported after a single usual therapeutic dose, the doses of isoprenaline giving the same bronchodilator effect must be multiplied by 32.6, 5.51, 4.63, 2.82 and 1.95 respectively with propranolol, diacetolol, acebutolol, atenolol, and bisoprolol. It was concluded that (1) atenolol and bisoprolol were the least potent drugs at bronchial level in therapeutic plasma concentrations and (2) that tests performed on the human isolated bronchus might be a useful screening procedure for new drugs with potential activity on the airways.

An Exploratory Study in Healthy Male Subjects of the Mechanism of Mirabegron‐Induced Cardiovascular Effects

“…As the median plasma t max for bisoprolol occurred at approximately 3 hours and for propranolol 5 to 6 hours postdose, simultaneous administration allowed for an effective blockade of the receptors. Maximum mean plasma concentrations for bisoprolol were in the same range as previously reported by others . On both study days, stable concentrations of bisoprolol were observed from 3 to 6 hours postdose.…”

Use of Propranolol Blockade to Explore the Pharmacology of GSK961081, a Bi-Functional Bronchodilator, in Healthy Volunteers: Results from Two Randomized Trials

“…For study 1, a dose of propranolol 80 mg 6 hourly (five doses in periods 1–4 and two doses in periods 5 and 6) was selected. Using published propranolol information on its pharmacokinetics in humans [ 22 ] and its in vitro affinity for the β2 receptor (pA2 = 9.4, competitive antagonist [ 23 ]), various propranolol dosing scenarios were simulated using Berkeley Madonna version 8.3.14 to determine a dosing regimen to maintain plasma propranolol concentrations above the in vitro predicted 90 % effective concentration (EC 90 ). The final propranolol dosing regimen selection was based on clinical safety experience [ 24 ] and the simulated scenarios, and allowed for the dosing interval of propranolol to be increased from once every 6 h to once every 8 h if tolerability issues arose.…”

Pharmacological actions of the selective and non‐selective β‐adrenoceptor antagonists celiprolol, bisoprolol and propranolol on human bronchi

“…Comparison of the compounds studied showed that the 0-adrenoceptor affinity of propranolol was significantly higher (K1: 0.0006 ttmol 1'-), than that of bisoprolol (K1: 0.4 gLmol 1-) and celiprolol (K1: 2.8 ptmol 1'). Therefore, the rank order of affinity is propranolol > bisoprolol > celiprolol resulting in relative affinities of 4667: 7: 1. tration: 0.289 ± 0.006 jtmol I', Naline et al, 1990) inhibited the isoprenaline effect on human bronchi by about 58%; 10 mg bisoprolol (plasma concentration: 0.15±0.006 jimol ['1;Naline et al, 1990) antagonized the isoprenaline effect by about 5% and 200 mg celiprolol (plasma concentration:…”

“…In order to evaluate further the clinical relevance of these data, the plasma concentrations resulting from oral doses of propranolol, 80 mg (Naline et al, 1990), bisoprolol, 1O mg (Naline et al, 1990) and celiprolol, 200 mg (Schmidt et al, 1985) were compared with the functional effects which had been evoked at those concentrations on intact preparations of human bronchi in vitro. This approach allowed the detection of an apparent difference between the PI-selective and the non-selective P-adrenoceptor antagonists.…”