Comparative biophysical analysis of the interaction of bronchodilating β2-adrenoceptor agonists with lipid membranes

Abstract

Two selective β2-adrenoceptor agonists, formoterol and salmeterol, have recently become commercially available. After inhalation of appropriate doses, both bronchodilators are capable of inducing a sustained relaxation of airway smooth muscle for =12 h. Remarkably, formoterol has a higher potency and shows a faster onset of relaxation than salmeterol. In this paper, evidence is presented that the long-acting relaxant effect of these drugs primarily results from an accumulation within plasmalemma lipid bilayers of airway smooth muscle and that the delayed response of salmeterol is due to its higher lipophilicity. Once having partitioned into the membrane lipid bilayer, the drugs remain trappe..