Effect of indacaterol, a novel long-acting beta 2-agonist, on human isolated bronchi

¹ Research Unit EA220, Université de Versailles, Faculté de Médecine, Pharmacology, Hôpital Foch, 40 rue Worth, 92150 Suresnes, France
² Novartis Institute for BioMedical Research, Horsham, England
³ Département de Pharmacologie, Université Victor Segalen Bordeaux 2; CHU Pellegrin, INSERM U657, Bordeaux, France

^* To whom correspondence should be addressed. E-mail: mathieu.molimard{at}pharmaco.u-bordeaux2.fr.

	Abstract

Indacaterol is a novel ₂-adrenoceptor agonist in development for the once-daily treatment of asthma and COPD. This study evaluated the relaxant effect of indacaterol on isolated human bronchi obtained from lungs of patients undergoing surgery for lung carcinoma.

Potency (-logEC₅₀), intrinsic efficacy (E_max) 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 E_max values were, respectively, 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.

In contrast to salmeterol, indacaterol did not antagonize the isoprenaline response. Indacaterol's onset of action (in minutes) (7.8±0.7) was not significantly different from that of formoterol (5.8±0.7) or salbutamol (11.0±0.4) but significantly faster than that of salmeterol (19.4±4.3). 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 over 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 ₂-adrenoceptor agonist with high intrinsic efficacy and fast onset of action.

Keywords:  Airways smooth muscle, ₂-adrenoceptor agonists, formoterol, indacaterol, isolated human bronchus, salmeterol

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