Effect of indacaterol, a novel long-acting beta2-agonist, on isolated human bronchi.
Indacaterol is a novel beta2-adrenoceptor agonist in development for the once-daily treatment of asthma and chronic obstructive pulmonary disease. The present study evaluated the relaxant effect of indacaterol on isolated human bronchi obtained from lungs of patients undergoing surgery for lung carcinoma. Potency (-logEC50), maximal relaxant effect (Emax) and onset of action were determined at resting tone. Duration of action was determined against cholinergic neural contraction induced by electrical field stimulation (EFS). At resting tone, -logEC50 and Emax values were 8.82+/-0.41 and 77+/-5% for indacaterol, 9.84+/-0.22 and 94+/-1% for formoterol, 8.36+/-0.16 and 74+/-4% for salmeterol, and 8.43+/-0.22 and 84+/-4% for salbutamol, respectively. In contrast to salmeterol, indacaterol did not antagonise the isoprenaline response. Indacaterol's onset of action (7.8+/-0.7 min) was not significantly different from that of formoterol (5.8+/-0.7 min) or salbutamol (11.0+/-4.0 min), but it was significantly faster than that of salmeterol (19.4+/-4.3 min). EFS-induced contractions were inhibited with -logIC50 values of 6.96+/-0.13 (indacaterol), 8.96+/-0.18 (formoterol), 7.18+/-0.34 (salmeterol) and 6.39+/-0.26 (salbutamol). Duration of action was >12 h for indacaterol and salmeterol, and 35.3+/-8.8 and 14.6+/-3.7 min for formoterol and salbutamol, respectively. In isolated human bronchi, indacaterol behaved as a long-acting beta2-adrenoceptor agonist with high intrinsic efficacy and fast onset of action.
Naline
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Research Unit EA220, Faculty of Medicine, Versailles University, Hospital Foch, Suresnes, France.
Trifilieff
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Fairhurst
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Advenier
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Molimard
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects*; D015363:Quinolones / Q000494:pharmacology*; D000068299:Salmeterol Xinafoate; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D007189:Indans; D015363:Quinolones; D000068299:Salmeterol Xinafoate; C510790:indacaterol; D007545:Isoproterenol; D000420:Albuterol; D000068759:Formoterol Fumarate