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.
Lindén
A
A
Division of Pulmonary Medicine, Sahlgrenska Hospital, University of Gothenburg, Sweden.
Rabe
K F
KF
Löfdahl
C G
CG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D001993:Bronchodilator Agents / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D000068299:Salmeterol Xinafoate; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate