Effect of inclacaterol, a novel long-acting β2-agonist, on isolated human bronchi

Indacaterol is a novel beta(2)-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 (-logEC(50)), 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, -logEC(50) 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 -logIC(50) 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 beta(2)-adrenoceptor agonist with high intrinsic efficacy and fast onset of action.