title: Allosteric activators of muscarinic receptors as novel approaches for treatment of CNS disorders.
abstract: Muscarinic acetylcholine receptors (mAChRs) represent exciting therapeutic targets for the treatment of multiple CNS disorders. The high degree of conservation of amino acids comprising the orthosteric acetylcholine (ACh) binding site between individual mAChR subtypes has hindered the development of subtype-selective compounds that bind to this site. As a result, many academic and industry researchers are now focusing on developing allosteric activators of mAChRs including both positive allosteric modulators (PAMs) and allosteric agonists. In the past 10 years major advances have been achieved in the discovery of allosteric ligands that possess much greater selectivity for individual mAChR subtypes when compared to previously developed orthosteric agents. These novel allosteric modulators of mAChRs may provide therapeutic potential for treatment of a number of CNS disorders such as Alzheimer's disease and schizophrenia.
authors.affiliation: gregory.j.digby@vanderbilt.edu
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Digby
authors.forename: Jana K
authors.initials: JK
authors.lastname: Shirey
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology*; D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D006801:Humans; D008954:Models, Biological; D018721:Muscarinic Agonists / Q000145:classification / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D011976:Receptors, Muscarinic / Q000378:metabolism
chemical_list: D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic