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Indacaterol: Ultra LABA Selection and Properties - A Pharmacologic Viewpoint

Trifilieff A.

RDD Europe 2011. Volume 1, 2011: 21-28.

Abstract:

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease, usually caused by tobacco smoke, involving inflammation, dysregulation of mucus production, destruction of lung parenchyma and systemic effects. All of these contribute to airflow limitation and gas exchange. Indacaterol, previously known as QAB149, is a novel, chirally - pure, inhaled beta2-adrenoceptor agonist. The molecule was discovered in a program designed to identify compounds for topical delivery with a fast onset of action, a duration compatible with once-daily dosing in man and an increased therapeutic index compared to the presently marketed inhaled beta2-adrenoceptor agonists. Pre-clinical profiling has shown that indacaterol is an agonist with high intrinsic efficacy, nanomolar potency and a good selectivity profile for beta2- versus the beta1- and beta3-adrenoceptors. These characteristics were studied in various in vitro and in vivo models. Indacaterol’s duration is believed to be due to its lipophilicity and specific strong interaction with the lipid raft component of the cell membrane. Its fast onset may be due to its higher intrinsic efficacy when compared with salmeterol. At a dose providing equivalent bronchoprotection, the drug was also shown to have a better cardiovascular safety profile in the rhesus monkey than either formoterol or salmeterol. These characteristics have been confirmed in clinical studies. Indacaterol has presently been approved for marketing in 46 countries, including Europe, for the long term treatment of COPD.