BRONCHOPROTECTION BY SALMETEROL - CELL STABILIZATION OR FUNCTIONAL ANTAGONISM - COMPARATIVE EFFECTS ON HISTAMINE-INDUCED AND AMP-INDUCED BRONCHOCONSTRICTION

Salmeterol provides bronchoprotection against a number of constrictor stimuli for more than 12 h after a single dose. This effect could be d ue either to functional antagonism at the level of airway smooth muscl e or to cell-stabilizing effects of the compound. In this study, we at tempted to clarify this mechanism by comparing the effects of salmeter ol (50 mu g), salbutamol (200 mu g) and placebo on the airway responsi veness to histamine (to assess functional antagonism), and to adenosin e 5'-monophosphate (AMP) (to assess additional cell-stabilizing effect s), 14 h after drug treatment. Thirteen patients with mild allergic as thma were studied in a double-blind, randomized protocol on 6 days, at least 48 h apart, Forced expiratory volume in one second (FEV(1)) was measured before and 15 min after inhalation of the study medication. Then, 14 h later (8 a.m. the following morning), a bronchoprovocation test with histamine or AMP was performed. We found that 14 h after inh alation, salmeterol still had a significant effect on FEV, in comparis on to placebo and salbutamol. The provocative dose producing a 20% fal l in FEV(1) (PD20 histamine) was significantly increased after salmete rol, whilst the increase in PD(20)AMP did not reach significance. The shift in PD20 (in doubling dose steps) induced by salmeterol pretreatm ent was not different between histamine and AMP. We conclude that the prolonged protective effect of salmeterol occurs via an extended bronc hodilating and functional antagonistic action and not via a cell-stabi lizing effect.