Relaxant effects and durations of action of formoterol and salmeterol on 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 isolated human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Potency (-log of the concentration of drug inducing 50% of maximal relaxation (-log EC50)) and efficacy (maximal effect (Emax), % of response to theophylline 3 x 10(-3) mol.l-1) were determined by analysis of cumulative isometric concentration-response curves to beta 2-adrenoceptor agonists in bronchial rings at resting tone or contracted maximally with acetylcholine 10(-3) mol.l-1 to induce functional antagonism. The onset and duration of action of beta-adrenoceptor agonists were measured by assessing the relaxant activity of drugs on the basal tone of isolated bronchi. In terms of potency, the rank order of the substances studied was formoterol > fenoterol > or = salmeterol > or = isoprenaline > or = salbutamol > or = adrenaline > or = terbutaline. Formoterol was 150-200 times more potent than isoprenaline. On preparations contracted with acetylcholine 10(-3) mol.l-1 the intrinsic activity (IA) of salbutamol, terbutaline and salmeterol compared with that of isoprenaline ranged 0.62-0.66. Intrinsic activity was higher 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 of salmeterol (6.40 +/- 1.40 min, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
Naline
E
E
Département de Pharmacologie, Faculté de Médecine, Paris, France.
Zhang
Y
Y
Qian
Y
Y
Mairon
N
N
Anderson
G P
GP
Grandordy
B
B
Advenier
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006801:Humans; D066298:In Vitro Techniques; D000068299:Salmeterol Xinafoate; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate; D004837:Epinephrine