Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development

Nat Rev Drug Discov. 2007 Sep;6(9):721-33. doi: 10.1038/nrd2379.


Muscarinic acetylcholine receptors (mAChRs), M(1)-M(5), regulate the activity of numerous fundamental central and peripheral functions. The lack of small-molecule ligands that can block or activate specific mAChR subtypes with high selectivity has remained a major obstacle in defining the roles of the individual receptor subtypes and in the development of novel muscarinic drugs. Recently, phenotypic analysis of mutant mouse strains deficient in each of the five mAChR subtypes has led to a wealth of new information regarding the physiological roles of the individual receptor subtypes. Importantly, these studies have identified specific mAChR-regulated pathways as potentially novel targets for the treatment of various important disorders including Alzheimer's disease, schizophrenia, pain, obesity and diabetes.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Drug Design*
  • Ligands
  • Mice
  • Mice, Knockout*
  • Muscarinic Agonists* / chemistry
  • Muscarinic Agonists* / pharmacology
  • Muscarinic Agonists* / therapeutic use
  • Muscarinic Antagonists* / chemistry
  • Muscarinic Antagonists* / pharmacology
  • Muscarinic Antagonists* / therapeutic use
  • Receptors, Muscarinic* / genetics
  • Receptors, Muscarinic* / metabolism
  • Receptors, Muscarinic* / physiology


  • Ligands
  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Receptors, Muscarinic