RELAXANT EFFECTS AND DURATIONS OF ACTION OF FORMOTEROL AND SALMETEROLON THE ISOLATED HUMAN BRONCHUS

The objective of this study was to evaluate the potency and efficacy ( intrinsic activity) of formoterol and salmeterol and their duration of action in comparison with other beta-adrenoceptor agonists in isolate d human bronchi. Human bronchi were obtained at thoracotomy from patie nts with lung cancer. Potency (-log of the concentration of drug induc ing 50% of maximal relaxation (log EC(50))) and efficacy (maximal effe ct (Emax), % of response to theophylline 3x10(-3) mol.l(-1)) determine d by analysis of cumulative isometric concentration-response curves to beta(2)-adrenoceptor agonists in bronchial rings at resting tone or c ontracted maximally with acetylcholine 10(-3) mol.l(-1) to induce func tional antagonism. The onset and duration of action of beta-adrenocept or agonists were measured by assessing the relaxant activity of drugs on the basal tone of isolated bronchi. In terms of potency, the rank o rder of the substances studied was formoterol > fenoterol greater than or equal to salmeterol greater than or equal to isoprenaline T salbut amol greater than or equal to adrenaline greater than or equal to terb utaline. Formoterol was 150-200 times more potent than isoprenaline. O n preparations contracted with acetylcholine 10(-3) mol.l(-1) the intr insic activity (IA) of salbutamol, terbutaline and salmeterol compared with that of isoprenaline ranged 0.62-0.66. Intrinsic activity was hi gher with formoterol (0.84) and fenoterol (0.75). The onset of action of formoterol (2.14+/-0.55 min, n=11) was not significantly different from that of salbutamol (1.90+/-0.24 min, n=8) but shorter than that o f salmeterol (6.40+/-1.40 min, n=10). The duration of action of formot erol was approximatively 4.5 fold longer than that of salbutamol; but, under similar conditions, salmeterol was more than 24 fold longer act ing than salbutamol. Formoterol appears to be a very potent and long-a cting beta-adrenoceptor agonist, with fast onset of effect on the isol ated human bronchus model. However, its duration of action, in vitro, was found to be shorter than that of salmeterol.