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

Abstract

1 The effects of salmeterol, a novel long‐acting β₂‐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 β‐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.