Effect of pretreatment with the selective beta 1-adrenoceptor antagonist bisoprolol on the subsequent cardiovascular actions and beta-adrenoceptor subtype specific occupancy of celiprolol in healthy man

Eur J Clin Pharmacol. 1993;44(4):341-8. doi: 10.1007/BF00316470.

Abstract

The cardiovascular effects at rest and during exercise and beta 1- and beta 2-adrenoceptor occupancy following a single dose of 1200 mg celiprolol p.o. were investigated in 8 healthy subjects with or without pretreatment with a single dose of 20 mg bisoprolol p.o., using a placebo-controlled, 2-way cross-over design. The ergometric responses of heart rate (HR) and systolic blood pressure (SBP) after celiprolol were reduced to a similar extent as after bisoprolol, but the cardiovascular function at rest was affected in a different way: there was a rise in HR, clear enhancement of cardiac systolic performance, and a considerable drop in the estimated total peripheral vascular resistance, associated with median beta 1-RRA and beta 2-RRA occupancies of 88 and 34%, respectively. The cardiovascular effects of celiprolol were not affected by pretreatment with bisoprolol. Celiprolol thus binds extensively to beta 1-adrenoceptors, moderately to beta 2-adrenoceptors, acts as beta 1-adrenergic antagonist (exemplified by the ergometric effects) but has vasodilator, positive chronotropic and cardiac systolic performance enhancing properties, which do not involve either direct or indirect beta 1-adrenergic agonism, but which might reflect beta 2-adrenergic agonism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Bisoprolol / pharmacology*
  • Cardiovascular System / drug effects*
  • Celiprolol / metabolism
  • Celiprolol / pharmacology*
  • Double-Blind Method
  • Drug Interactions
  • Exercise Test
  • Humans
  • Male
  • Radioligand Assay
  • Receptors, Adrenergic, beta / metabolism
  • Reference Values
  • Time Factors

Substances

  • Receptors, Adrenergic, beta
  • Celiprolol
  • Bisoprolol