Salmeterol: a potent and long-acting inhibitor of inflammatory mediator release from human lung

Br J Pharmacol. 1991 Nov;104(3):672-6. doi: 10.1111/j.1476-5381.1991.tb12487.x.

Abstract

1. The effects of salmeterol, a novel long-acting beta 2-adrenoceptor agonist, have been investigated on antigen-induced mediator release from passively sensitized fragments of human lung in vitro. 2. Salmeterol was a potent inhibitor of the release of histamine (-log IC50 = 8.54), leukotriene C4 (LTC4)/LTD4 (-log IC50 = 9.07) and prostaglandin D2 (-log IC50 = 8.81). It was slightly less potent (1-3 fold) than isoprenaline, but significantly more potent (10-35 fold) than salbutamol. 3. Propranolol competitively antagonized the inhibitory effects of salmeterol on histamine release (pA2 = 8.41) and LTC4/LTD4 release, (pA2 = 8.40) indicating an action via beta-adrenoceptors. 4. The inhibitory effects of isoprenaline (20 nM) and salbutamol (200 nM) were removed after washing the lung tissue for 2 h and 4 h respectively. In contrast, the inhibitory effects of salmeterol (40 nM) were much longer-lasting, and were still evident after 20 h. 5. Salmeterol therefore exhibits potent and persistent inhibition of anaphylactic mediator release from human lung. This anti-inflammatory effect may be important for the therapeutic potential of salmeterol in the treatment of bronchial asthma.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / analogs & derivatives*
  • Albuterol / pharmacology
  • Histamine Release / drug effects
  • Humans
  • Hypersensitivity / metabolism
  • In Vitro Techniques
  • Inflammation / physiopathology*
  • Lung / drug effects
  • Lung / metabolism*
  • Mast Cells / drug effects
  • Mast Cells / metabolism
  • Propranolol / pharmacology
  • Prostaglandin D2 / metabolism
  • SRS-A / metabolism
  • Salmeterol Xinafoate

Substances

  • Adrenergic beta-Agonists
  • SRS-A
  • Salmeterol Xinafoate
  • Propranolol
  • Albuterol
  • Prostaglandin D2