LONG-ACTING AND SHORT-ACTING BETA(2) ADRENOCEPTOR AGONISTS - INTERACTIONS IN HUMAN CONTRACTED BRONCHI

The aim of this study was to systematically compare the interaction of the long-acting beta(2)-adrenoceptor agonists formoterol and salmeter ol with short-acting beta(2)-adrenoceptor agonists in contracted human bronchi. Human bronchi were obtained at thoracotomy from patients wit h lung cancer. Formoterol or salmeterol at concentrations inducing up to 92 and 94% of their maximal relaxant effect, respectively, were add ed to bronchial rings contracted with carbachol (10(-6)M), After a tim e period of 30 min, concentration-response curves far the short-acting beta(2)-adrenoceptor agonists, salbutamol, terbutaline, isoprenaline and fenoterol were recorded. Administration of equieffective concentra tions of salmeterol and formoterol, resulted in only salmeterol induci ng a shift to the right of isoprenaline, terbutaline, fenoterol and sa lbutamol concentration-response curves. The rank order of shift was sa lbutamol > fenoterol > terbutaline > isoprenaline. Formoterol, up to c oncentrations of 3 x 10(-9) M induced submaximal relaxation resulting in no shift in short-acting beta(2)-adrenoceptor agonist concentration -response curves. Salmeterol but not formoterol appears to antagonize the relaxation of human contracted bronchi induced by short-acting bet a(2)-agonists. These results obtained in vitro cannot be translated in clinical terms. This study, however, highlights the need for clinical studies on the interaction of long-acting and short-acting beta(2)-ad renoceptor agonists in acute severe asthma.