title: Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.
abstract: Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-α and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases.
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Khuder
authors.initials: K
authors.lastname: Alagha
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Palot
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Tunde
authors.initials: T
authors.lastname: Sofalvi
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Laurie
authors.initials: L
authors.lastname: Pahus
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gouitaa
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Tummino
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Martinez
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Charpin
authors.affiliation: Respiratory Department, Arnaud de Villeneuve Hospital, Montpellier, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bourdin
authors.affiliation: Respiratory Department, AP-HM, Inserm CNRS U 1067, UMR7333, Aix Marseille Université, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
keywords: aclidinium bromide; asthma; chronic obstructive pulmonary disease; glycopyrronium bromide; long-acting muscarinic receptor antagonists; tiotropium bromide