Long- and short-acting beta2 adrenoceptor agonists: interactions in human contracted bronchi.
The aim of this study was to systematically compare the interaction of the long-acting beta2-adrenoceptor agonists formoterol and salmeterol with short-acting beta2-adrenoceptor agonists in contracted human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Formoterol or salmeterol at concentrations inducing up to 92 and 94% of their maximal relaxant effect, respectively, were added to bronchial rings contracted with carbachol (10(-6) M). After a time period of 30 min, concentration-response curves for the short-acting beta2-adrenoceptor agonists, salbutamol, terbutaline, isoprenaline and fenoterol were recorded. Administration of equieffective concentrations of salmeterol and formoterol, resulted in only salmeterol inducing a shift to the right of isoprenaline, terbutaline, fenoterol and salbutamol concentration-response curves. The rank order of shift was salbutamol > fenoterol > terbutaline > isoprenaline. Formoterol, up to concentrations of 3x10(-9) M induced submaximal relaxation resulting in no shift in short-acting beta2-adrenoceptor agonist concentration-response curves. Salmeterol but not formoterol appears to antagonize the relaxation of human contracted bronchi induced by short-acting beta2-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 beta2-adrenoceptor agonists in acute severe asthma.
Molimard
M
M
Dépt de Pharmacologie, CHU Pellegrin-Carreire, Bordeaux, France.
Naline
E
E
Zhang
Y
Y
Le Gros
V
V
Begaud
B
B
Advenier
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D000068299:Salmeterol Xinafoate; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D002217:Carbachol; D000420:Albuterol; D000068759:Formoterol Fumarate