Pharmacological basis for duration of effect: Formoterol and salmeterol versus short-acting beta(2)-adrenoceptor agonists

The mechanisms behind the long duration of bronchodilating action of the beta(2)-adrenoceptor agonists formoterol and salmeterol are only partially understood, This review compares pharmacological characteristics of long-acting versus short-acting beta(2)-adrenoceptor agonists in human and animal airways. Based upon the reviewed evidence, it is concluded that for beta(2)-adrenoceptor agonists, long duration of action may depend upon several factors, Both formoterol and salmeterol display a higher lipophilicity and have a higher affinity, selectivity, and potency than most short-acting agonists at the beta(2)-adrenoceptor. Of these factors, lipophilicity may prove to be one of the most important ones by determining the amount of drug entering into the cell membrane in the vicinity of the beta(2)-adrenoceptor. However, the receptor affinity, maximal relaxant effect (efficacy or intrinsic activity), potency, and receptor selectivity may also be of importance in determining how much beta(2)-adrenoceptor agonist must remain at the receptor for sustained action.