title: Inhaled muscarinic antagonists for respiratory diseases: a review of patents and current developments (2006 - 2010).
abstract: BACKGROUND
  Because tiotropium has demonstrated clinical benefits as a long-term maintenance treatment for chronic obstructive pulmonary disease (COPD), the number of patent applications of new chemical entities with antimuscarinic activity has significantly increased, along with the number of compounds that have reached clinical development.
  
  
  METHODS
  This review summarizes the current status of long-acting muscarinic antagonists (LAMA) in clinical development for COPD, and the associated patent literature since 2006, with a focus on new chemical entities.
  
  
  CONCLUSIONS
  In recent years, companies have taken different approaches to obtain compounds with high potency, long duration of action and minimal systemic exposure. Several strategies for minimizing adverse effects due to systemic exposure have been identified (quaternization, higher rate of plasma hydrolysis and degradation, increased plasma protein binding). The beneficial effects beyond bronchodilation that may be provided in the treatment of COPD patients with a LAMA, and the advantages of combination therapies, such as LAMA + LABA and LAMA + corticosteroids, have also been taken into account in recent studies.
authors.affiliation: Almirall R&D Centre, Department of Medicinal Chemistry, Treball 2-4, 08960 Sant Just Desvern, Barcelona, Spain. maria.prat@almirall.com
authors.forename: Maria
authors.initials: M
authors.lastname: Prat
authors.forename: Amadeu
authors.initials: A
authors.lastname: Gavaldà
authors.forename: Silvia
authors.initials: S
authors.lastname: Fonquerna
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miralpeix
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D003692:Delayed-Action Preparations; D015195:Drug Design; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010330:Patents as Topic; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000318:Adrenergic beta-Agonists; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D018727:Muscarinic Antagonists