Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development.
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.
Wess
Jürgen
J
Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA. jwess@helix.nih.gov
Eglen
Richard M
RM
Gautam
Dinesh
D
D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D008024:Ligands; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic