title: A dose-ranging study to evaluate the beta-adrenoceptor selectivity of single doses of betaxolol.
abstract: 1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 20 mg (B20), 40 mg (B40), 80 mg (B80), propranolol 40 mg (P40), or placebo (PL) in a single-blind randomised cross-over design. 2. beta 1-adrenoceptor blockade was assessed by reductions in exercise heart rate. Betaxolol produced dose-related reductions in exercise heart rate (beats min-1) up to a ceiling at B40, after which B80 showed a lesser effect: (158 +/- 8 PL, 128 +/- 3 B10, 123 +/- 2 B20, 116 +/- 4 B40, 136 +/- 10 B80, 135 +/- 4 P40). All doses of betaxolol (except B80) produced greater reductions compared with P40: (B10 P less than 0.001, B20 P less than 0.005, B40 P less than 0.001). 3. beta 2-adrenoceptor blockade was assessed by attenuation of finger tremor and cardiovascular responses to graded infusions of i.v. isoprenaline. Dose-response curves were constructed and the doses required to increase heart rate by 25 beats min-1, finger tremor by 200%, calf blood flow by 0.5 ml dl-1 min-1, and decrease diastolic blood pressure by 10 mm Hg, after each treatment were calculated. These were then compared with placebo responses and expressed as dose-ratios. 4. Dose-ratios for finger tremor showed significant attenuation by all doses of betaxolol (compared with PL): B10 1.5 +/- 0.18 (P less than 0.05), B20 2.62 +/- 0.45 (P less than 0.005), B40 2.55 +/- 0.33 (P less than 0.001), B80 2.48 +/- 0.48 (P less than 0.01); and by P40 6.49 +/- 1.12 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
authors.forename: N A
authors.initials: NA
authors.lastname: Irvine
authors.forename: B J
authors.initials: BJ
authors.lastname: Lipworth
authors.forename: D G
authors.initials: DG
authors.lastname: McDevitt
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D015784:Betaxolol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007866:Leg / Q000098:blood supply; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D014202:Tremor / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol; D015784:Betaxolol