The Preclinical Pharmacology of Indacaterol

The preclinical pharmacological profile of indacaterol, a novel, chirally pure inhaled beta(2) adrenoceptor agonist, is described in this chapter. In various in vitro systems, indacaterol is close to a full agonist at the human β2-adrenoceptor with nanomolar potency. In isolated superfused human and guinea pig trachea, indacaterol has a fast onset of and a long duration of action. In the conscious guinea pig, when given intratracheally as a dry powder, indacaterol inhibits bronchoconstriction for at least 24 h and shows no tachyphylaxis when given for 5 consecutive days. When given via nebulization to anesthetized rhesus monkeys, indacaterol produces a prolonged bronchoprotective effect and induces a small increase in heart rate. In in vitro systems as well as a large cohort of COPD patients, no association could be demonstrated between β2-adrenoceptor polymorphisms and indacaterol response. In conclusion, the preclinical profile of indacaterol suggests that this compound has a duration of action compatible with once-daily dosing in human, together with a fast onset of action.