title: Long-acting muscarinic receptor antagonists for the treatment of respiratory disease.
abstract: The use of muscarinic receptor antagonists in the treatment of chronic obstructive pulmonary disease (COPD) is well established. More recently, the potential for long-acting muscarinic receptor antagonists (LAMAs) in the treatment of asthma has also been investigated. While LAMAs offer advantages over short-acting muscarinic receptor antagonists, in terms of a reduced dosing frequency, there remains a need for therapies that improve symptom control throughout both the day and night, provide better management of exacerbations and deliver improved health-related quality of life. Furthermore, the potential for unwanted anticholinergic side effects, particularly cardiovascular effects, remains a concern for this class of compounds. Novel LAMAs in clinical development for the treatment of respiratory disease include: aclidinium bromide, NVA237 (glycopyrronium bromide), GP-MDI, EP-101, CHF-5259, umeclidinium bromide, CHF-5407, TD-4208, AZD8683 and V-0162. These compounds offer potential advantages in terms of onset of action, symptom control and safety. In addition, a number of LAMAs are also being developed as combination treatments with long-acting β2-agonists (LABAs) or inhaled glucocorticosteroids, potentially important treatment options for patients who require combination therapy to achieve an optimal therapeutic response as their disease progresses. More recently, compounds such as GSK961081 and THRX-198321 have been identified that combine LAMA and LABA activity in the same molecule, and have the potential to offer the benefits of combination therapy in a single compound. Here, we review novel LAMAs and dual action compounds in clinical development, with a particular focus on how they may address the current unmet clinical needs in the treatment of respiratory disease, particularly COPD.
authors.affiliation: Unit of Respiratory Clinical Pharmacology, Department of System Medicine, University of Rome 'Tor Vergata', 00133 Rome, Italy. mcazzola@qubisoft.it
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Clive
authors.initials: C
authors.lastname: Page
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009330:Nebulizers and Vaporizers; D011788:Quality of Life
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005938:Glucocorticoids; D018727:Muscarinic Antagonists