COMPARISON OF THE ANTIINFLAMMATORY PROPERTIES OF FORMOTEROL, SALBUTAMOL AND SALMETEROL IN GUINEA-PIG SKIN AND LUNG

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 mug ml-1) inhibited histamine-induced plasma protein extravasation (PPE) in guinea-pig lung, with significant inhibition being observed at 10 and 100 mug ml-1. Formoterol (100 mug 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 mug ml-1) and salmeterol (100 mug 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.