Multivalent dual pharmacology muscarinic antagonist and β₂ agonist (MABA) molecules for the treatment of COPD.

Abstract Inhaled beta-2-adrenergic receptor (β 2 ) agonists and inhaled muscarinic acetylcholine antagonists are the most frequently used bronchodilators in the treatment of chronic obstructive pulmonary disease. While short-acting agents (4–6 h) serve as ‘rescue’ therapy, long-acting (12–24 h) bronchodilators can reduce the incidence and number of exacerbations as well as improve lung function. Due to the complementary nature of the two mechanisms, combinations of the two classes provide even greater improvement in lung function than either mechanism alone. This review focuses on the multivalent origins of dual pharmacology MABA bronchodilators and describes the supporting in vitro characterization and reported animal studies. Topics discussed include approaches taken to identify novel MABA molecules, highlighting preferred muscarinic and β 2 -binding groups and how these two entities are linked together; challenges in designing MABA molecules; and the potential benefits of enhanced bronchoprotection and opportunity for ‘triple therapy’ with an inhaled corticosteroid.