Inhaled long-acting β2-adrenoceptor agonists (LABAs) are central in the symptomatic management of chronic obstructive pulmonary disease (COPD). The two available compounds in this class are formoterol and salmeterol, both administered twice a day. The increasing prevalence and burden of COPD worldwide has stimulated a renewed interest in the development of novel drugs for the optimization of COPD management. In this perspective, once-daily β2-adrenoceptor agonists (ultra-LABAs) are in development, with improved duration and rapid onset of action, no antagonism of the bronchorelaxant effect of short-acting β2-agonists utilized as rescue medications, and a favourable safety profile. Among these new agents, indacaterol has been recently approved by the European Medicines Agency for maintenance bronchodilator treatment of airflow obstruction in adult patients with COPD. In preclinical studies, indacaterol showed a longer duration of action compared with other available β2-adrenergic bronchodilators, and a quick onset of action (similar to formoterol and much faster than salmeterol). These pharmacological properties are potentially explained by the unique lipophilic profile of indacaterol, which has a 2-fold greater affinity for membrane lipid rafts and a 2-fold faster association kinetic with lipid membranes compared to salmeterol. Moreover, indacaterol has an intrinsic efficacy in-between full (formoterol) and partial (salmeterol) agonist, and, like formoterol, does not antagonize isoprenaline effect on human bronchi, whereas salmeterol has a significat antagonist effect. Several trials have been conducted or are currently underway with the aim of evaluating the efficacy and safety of indacaterol in patients with COPD. Until now, these studies have shown that short-term treatment with indacaterol once daily improves pulmonary function as assessed by FEV, and inspiratory capacity, and have documented a favourable safety profile. Ongoing long-term studies will assess its effect on the progression of COPD. Overall, indacaterol has shown a unique pharmacological profile among the available LABA and offers a new therapeutic option for COPD.
|Translated title of the contribution||Pharmacology of long-acting β2-agonists for use in COPD: Similarities and differences|
|Number of pages||9|
|Journal||Rassegna di Patologia dell'Apparato Respiratorio|
|Publication status||Published - Feb 2010|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Pulmonary and Respiratory Medicine