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Comparison of the anti‐inflammatory properties of formoterol, salbutamol and salmeterol in guinea‐pig skin and lung
Author(s) -
Whelan C.J.,
Johnson M.,
Vardey C.J.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13855.x
Subject(s) - formoterol , salbutamol , guinea pig , formoterol fumarate , salmeterol , histamine , pharmacology , chemistry , extravasation , medicine , endocrinology , inhalation , anesthesia , immunology , asthma , budesonide
1 We have compared some anti‐inflammatory properties of formoterol, salbutamol and salmeterol in guinea‐pig skin and lung. 2 Intradermal formoterol (1 × 10 −10 to 1 × 10 −8 mol/site), salbutamol (1 × 10 −8 and 1 × 10 −7 mol/site) and salmeterol (1 × 10 −8 and 1 × 10 −7 mol/site) inhibited bradykinin‐induced plasma protein extravasation (PPE) in guinea‐pig skin. A maximally effective dose of formoterol (1 × 10 −9 mol/site) and salbutamol (1 × 10 −8 mol/site) inhibited PPE in guinea‐pig skin for 2–4 h and 1–2 h respectively, whereas salmeterol (1 × 10 −8 mol/site) was effective for >6 h. 3 Inhaled formoterol (nebuliser concentration 0.1 to 100 μg ml −1 ) inhibited histamine‐induced plasma protein extravasation (PPE) in guinea‐pig lung, with significant inhibition being observed at 10 and 100 μg ml −1 . Formoterol (100 μg 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 μg ml −1 ) and salmeterol (100 μg 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 β‐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 β 2 ‐adrenoceptor agonists may involve an action on β 2 ‐adrenoceptors on a cell type other than the endothelial cell.