%0 Journal Article %A Cliff Battram %A Steven J. Charlton %A Bernard Cuenoud %A Mark R. Dowling %A Robin A. Fairhurst %A David Farr %A John R. Fozard %A Juliet R. Leighton-Davies %A Christine A. Lewis %A Lorraine McEvoy %A Robert J. Turner %A Alexandre Trifilieff %T In Vitro and in Vivo Pharmacological Characterization of 5-[(R)-2-(5,6-Diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (Indacaterol), a Novel Inhaled β2 Adrenoceptor Agonist with a 24-h Duration of Action %D 2006 %R 10.1124/jpet.105.098251 %J Journal of Pharmacology and Experimental Therapeutics %P 762-770 %V 317 %N 2 %X Here, we describe the preclinical pharmacological profile of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (indacaterol), a novel, chirally pure inhaled β2 adrenoceptor agonist, in comparison with marketed drugs. Indacaterol is close to a full agonist at the human β2 adrenoceptor (Emax = 73 ± 1% of the maximal effect of isoprenaline; pEC50 = 8.06 ± 0.02), whereas salmeterol displays only partial efficacy (38 ± 1%). The functional selectivity profile of indacaterol over β1 human adrenoceptors is similar to that of formoterol, whereas its β3 adrenoceptor selectivity profile is similar to that of formoterol and salbutamol. In isolated superfused guinea pig trachea, indacaterol has a fast onset of action (30 ± 4 min) similar to formoterol and salbutamol, and a long duration of action (529 ± 99 min) comparable with salmeterol. In the conscious guinea pig, when given intratracheally as a dry powder, indacaterol inhibits 5-hydroxytryptamine-induced bronchoconstriction for at least 24 h, whereas salmeterol, formoterol, and salbutamol have durations of action of 12, 4, and 2 h, respectively. When given via nebulization to anesthetized rhesus monkeys, all of the compounds dose-dependently inhibit methacholine-induced bronchoconstriction, although indacaterol produces the most prolonged bronchoprotective effect and induces the lowest increase in heart rate for a similar degree of antibronchoconstrictor activity. In conclusion, the preclinical profile of indacaterol suggests that this compound has a superior duration of action compatible with once-daily dosing in human, together with a fast onset of action and an improved cardiovascular safety profile over marketed inhaled β2 adrenoceptor agonists. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/317/2/762.full.pdf