A dose-ranging study to evaluate the beta 1-adrenoceptor selectivity of bisoprolol.
A dose-ranging study was performed to compare the beta 1-adrenoceptor selectivity of bisoprolol with that of atenolol and nadolol. Seven normal subjects (mean age 26 y) were given single oral doses of bisoprolol 5 mg (B5), 10 mg (B10), 20 mg (B20); atenolol 50 mg (A50), 100 mg (A100); nadolol 40 mg (N40); and placebo (PL), in a single blind randomised cross-over design. Beta 2-adrenoceptor responses were assessed by attenuation of finger tremor and cardiovascular responses to graded isoprenaline infusions. Dose-response curves were constructed, and doses of isoprenaline required to increase finger tremor by 100% (IT100), heart rate by 25 beats/min (IH25), SBP by 25 mmHg (IS25), cardiac output by 35% (IC35), and decrease DBP by 10 mmHg (ID10), after each treatment were calculated. These indices were compared with placebo response and expressed as dose-ratios. Exercise heart rate (EHR) was used to assess beta 1-adrenoceptor blockade. There were dose-related increases in plasma concentrations of bisoprolol and atenolol. Reduction of EHR was significantly less with B5 (16.8%) in comparison with all other treatments: B10 21.9%, B20 23.1%; A50 22.5%, A100 22.6%; N40 22.9%. There were small but significant reductions in isoprenaline-induced tachycardia with bisoprolol and atenolol, although mean dose-ratios were considerably less in comparison with N40 (IH25 dose-ratios): B5 2.55, B10 3.18, B20 3.93, A50 2.91, A100 4.89, N40 17.23. There were similar patterns for the other isoprenaline responses. These results show that conventional doses of bisoprolol (10 mg) and atenolol (50 mg) produced equal antagonism of beta 1 and beta 2-adrenoceptors, and therefore possess equal degrees of beta 1-adrenoceptor selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipworth
B J
BJ
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, UK.
Irvine
N A
NA
McDevitt
D G
DG
D000319:Adrenergic beta-Antagonists; D000328:Adult; D000704:Analysis of Variance; D001262:Atenolol / Q000494:pharmacology; D017298:Bisoprolol; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D009248:Nadolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D016037:Single-Blind Method; D013223:Statistics as Topic; D014202:Tremor / Q000139:chemically induced
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D009248:Nadolol; D001262:Atenolol; D007545:Isoproterenol; D017298:Bisoprolol