Does a selective muscarinic receptor (M3) antagonist enhance the efficacy through oral delivery in chronic obstructive pulmonary disease patients?

Abstract

COPD is a syndrome characterised by progressive airflow limitation caused by chronic inflammation of the airways and lung parenchyma. It is the most common lung disease, carrying a significant mortality, morbidity and healthcare costs worldwide. COPD is associated with increased activity of parasympathetic nervous system that plays a dominant role in the regulation of airways tone. As cholinergic tone seems to be the only reversible component of COPD, muscarinic receptor antagonists (MRAs) represent the most effective class of bronchodilators in COPD. Thus MRAs remain the mainstay of pharmacotherapy in COPD as they increase expiratory flow rate by decreasing airway smooth muscle tone and mucus secretion leading to enhanced lung function. The discovery of the different muscarinic receptor subtypes that are involved in the regulation of airway function led to the development of more subtype-selective MRAs for the treatment of COPD. Furthermore, it has been hypothesised that the compounds preferentially antagonise the muscarinic M3 receptor-mediated effects would provide better clinical efficacy with a reduction in adverse events related to the blockade of other muscarinic receptor subtypes. Based on this hypothesis, the present multi-centre, randomised, placebo-controlled study assessed the effectiveness of selective muscarinic receptor (M3) antagonist through oral delivery in COPD patients.

Keywords::

• airways
• bronchodilation
• COPD
• muscarinic receptor antagonists