title: Muscarinic antagonists in early stage clinical development for the treatment of asthma.
abstract: Parasympathetic neurons utilize the neurotransmitter acetylcholine to modulate and constrict airway smooth muscles at the muscarinic acetylcholine receptor. Inhaled agents that antagonize the muscarinic (M) acetylcholine receptor, particularly airway M3 receptors, have increasing data supporting use in persistent asthma. Areas covered: Use of inhaled long-acting muscarinic antagonists (LAMA) in asthma is explored. The LAMA tiotropium is approved for maintenance in symptomatic asthma patients despite the use of inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRA) and/or long-acting beta2agonists (LABA). LAMA agents currently approved for chronic obstructive pulmonary disease (COPD) include tiotropium, glycopyrrolate/glycopyrronium, umeclidinium and aclidinium. These agents are reviewed for their pharmacological differences and clinical trials in asthma. Expert opinion: Current guidelines place inhaled LAMAs as adjunctive maintenance therapy in symptomatic asthma not controlled by an ICS and/or a LTRA. LAMA agents will play an increasing role in moderate to severe symptomatic asthma patients. Additional LAMA agents are likely to seek a maintenance indication perhaps as a combined inhaler with an ICS or with an ICS and a LABA. These fixed-dose combination inhalers are being tested in COPD and asthma patients. Once-a-day dosing of inhaled LAMA agents in severe asthma patients will likely become the future standard.
authors.affiliation: a Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine , School of Medicine, U.C. Davis , Sacramento , CA , USA.|b Department of Emergency Medicine , School of Medicine U. C. Davis , Sacramento , CA , USA.|c Department of Medicine , Veterans Administration Northern California Health Care System , Mather , CA , USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Albertson
authors.affiliation: b Department of Emergency Medicine , School of Medicine U. C. Davis , Sacramento , CA , USA.|c Department of Medicine , Veterans Administration Northern California Health Care System , Mather , CA , USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Chenoweth
authors.affiliation: a Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine , School of Medicine, U.C. Davis , Sacramento , CA , USA.
authors.forename: Jason Y
authors.initials: JY
authors.lastname: Adams
authors.affiliation: b Department of Emergency Medicine , School of Medicine U. C. Davis , Sacramento , CA , USA.|c Department of Medicine , Veterans Administration Northern California Health Care System , Mather , CA , USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sutter
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003692:Delayed-Action Preparations; D015195:Drug Design; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3
keywords: Asthma; aclidinium; glycopyrrolate; long-acting muscarinic antagonist (LAMA); tiotropium; umeclidinium