Formoterol: pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective beta 2-adrenoceptor agonist bronchodilator

Life Sci. 1993;52(26):2145-60. doi: 10.1016/0024-3205(93)90729-m.

Abstract

Formoterol is an innovative, highly potent, beta 2-adrenoceptor-selective agonist combining the clinical advantages of rapid onset of action with a duration of action in excess of 12 h. In vitro, formoterol is a potent airway smooth muscle relaxant with high efficacy, and very high affinity and selectivity for the beta 2-adrenoceptor. Formoterol appears to be retained in airway smooth muscle for extended periods since its relaxant effect on human airway smooth muscle is resistant to repeated washing and formoterol displays 'reassertion' of relaxation after washout of a beta-adrenoceptor antagonist. A model based on the diffusion microkinetics of formoterol into the plasmalemma lipid bilayer is proposed as a basis for these properties. In addition to the release of pro-inflammatory mediators from cells such as the mast cell, several other disease processes probably occur in asthma. Leukocytes, notably eosinophils, adhere to the vascular endothelium and emigrate into airway tissues, which may be damaged by these cells if they are activated to release mediators or their granular contents. Plasma and its component proteins are extravasated from the bronchial microcirculation. Formoterol has been demonstrated to potently inhibit these cells and processes in experimental test systems. Continuing clinical research involving histological examination of tissue reactions may allow a more complete determination of the effects of formoterol on inflammatory processes in humans and the clinical relevance of any such effects.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Agonists / pharmacokinetics
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Asthma / drug therapy
  • Asthma / metabolism
  • Bronchodilator Agents / pharmacokinetics
  • Bronchodilator Agents / pharmacology*
  • Ethanolamines / pharmacokinetics
  • Ethanolamines / pharmacology*
  • Formoterol Fumarate
  • Humans
  • Time Factors

Substances

  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Ethanolamines
  • Formoterol Fumarate