Reduction of exercise tachycardia in man after propranolol, atenolol and bisoprolol in comparison to beta-adrenoceptor occupancy

Eur Heart J. 1987 Dec:8 Suppl M:3-8. doi: 10.1093/eurheartj/8.suppl_m.3.

Abstract

In a double blind, placebo controlled study, propranolol (240 mg), atenolol (200 mg) or bisoprolol (100 mg) were administered as a single oral dose to groups of 6 healthy male volunteers. Exercise tachycardia was monitored for 84 hours after administration of the drugs to monitor beta blockade in vivo. Plasma samples drawn in parallel with these effects were used to detect beta 1- or beta 2-adrenoceptor occupancy in two subtype selective in vitro receptor binding assays. Reduction of exercise tachycardia parallels beta 1-adrenoceptor occupancy. Furthermore, at comparable beta 1-adrenoceptor occupancy, less beta 2-adrenoceptor occupancy was observed after bisoprolol than after atenolol. The latter finding is in agreement with the two-fold higher beta 1/beta 2-selectivity ratio of bisoprolol (75-fold) versus atenolol (35-fold). It is concluded, that beta blockade observed via the reduction of exercise tachycardia can be delineated from the in vitro occupancy of beta 1-adrenoceptors by an antagonist present in plasma samples.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / metabolism
  • Adrenergic beta-Antagonists / pharmacokinetics
  • Adult
  • Atenolol / administration & dosage
  • Atenolol / metabolism
  • Atenolol / pharmacokinetics
  • Bisoprolol
  • Double-Blind Method
  • Exercise Test*
  • Heart Rate / drug effects
  • Humans
  • Male
  • Propanolamines / administration & dosage
  • Propanolamines / metabolism
  • Propanolamines / pharmacokinetics
  • Propranolol / administration & dosage
  • Propranolol / metabolism
  • Propranolol / pharmacokinetics
  • Receptors, Adrenergic, beta / analysis
  • Receptors, Adrenergic, beta / classification
  • Receptors, Adrenergic, beta / drug effects*
  • Tachycardia / blood
  • Tachycardia / drug therapy*
  • Tachycardia / etiology

Substances

  • Adrenergic beta-Antagonists
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Atenolol
  • Propranolol
  • Bisoprolol