Comparison of the anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea-pig skin and lung

Br J Pharmacol. 1993 Oct;110(2):613-8. doi: 10.1111/j.1476-5381.1993.tb13855.x.

Abstract

1. We have compared some anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea-pig skin and lung. 2. Intradermal formoterol (1 x 10(-10) to 1 x 10(-8) mol/site), salbutamol (1 x 10(-8) and 1 x 10(-7) mol/site) and salmeterol (1 x 10(-8) and 1 x 10(-7) mol/site) inhibited bradykinin-induced plasma protein extravasation (PPE) in guinea-pig skin. A maximally effective dose of formoterol (1 x 10(-9) mol/site) and salbutamol (1 x 10(-8) mol/site) inhibited PPE in guinea-pig skin for 2-4 h and 1-2 h respectively, whereas salmeterol (1 x 10(-8) mol/site) was effective for > 6 h. 3. Inhaled formoterol (nebuliser concentration 0.1 to 100 micrograms ml-1 inhibited histamine-induced plasma protein extravasation (PPE) in guinea-pig lung, with significant inhibition being observed at 10 and 100 micrograms ml-1. Formoterol (100 micrograms ml-1) inhibited PPE in guinea-pig lung for 2-4 h, a duration of action intermediate between that previously obtained for salbutamol (1 h) and salmeterol (> 6 h). 4. Formoterol, like salbutamol, had no effect on neutrophil accumulation or granulocyte-dependent PPE (zymosan-induced) in guinea-pig skin. Formoterol inhibited neutrophil accumulation (lipopolysaccharide-induced) in guinea-pig lung but at doses greater than those required to inhibit granulocyte-independent PPE (histamine-induced). In contrast, salmeterol inhibited neutrophil accumulation and granulocyte-dependent PPE in guinea-pig skin and inhibited neutrophil accumulation in guinea-pig lung at doses which inhibit granulocyte-independent PPE. 5. Inhaled formoterol (nebuliser concentration 100 microg ml-1) and salmeterol (100 microg ml-1) both inhibited PAF-induced eosinophil accumulation in guinea-pig lung. However, unlike salmeterol, this effect of formoterol was observed only at suprabronchodilator doses.6. We conclude that to inhibit neutrophil accumulation, at doses which inhibit granulocyte-independent PPE, agonists acting at beta-adrenoceptors on vascular endothelium require a duration of action greater than that of salbutamol and formoterol. However, we speculate that the mechanism of inhibition of eosinophil accumulation in guinea-pig lung by beta2-adrenoceptor agonists may involve an action on beta2-adrenoceptors on a cell type other than the endothelial cell.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Albuterol / analogs & derivatives
  • Albuterol / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blood Proteins / metabolism
  • Bronchoalveolar Lavage Fluid / cytology
  • Ethanolamines / pharmacology
  • Formoterol Fumarate
  • Granulocytes / drug effects
  • Guinea Pigs
  • Histamine / pharmacology
  • Humans
  • In Vitro Techniques
  • Infant, Newborn
  • Lung / cytology
  • Lung / drug effects*
  • Male
  • Neutrophils / drug effects
  • Platelet Activating Factor / pharmacology
  • Receptors, Adrenergic, beta-2 / drug effects*
  • Salmeterol Xinafoate
  • Skin / cytology
  • Skin / drug effects*

Substances

  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Proteins
  • Ethanolamines
  • Platelet Activating Factor
  • Receptors, Adrenergic, beta-2
  • Salmeterol Xinafoate
  • Histamine
  • Albuterol
  • Formoterol Fumarate