Muscarinic acetylcholine receptors as CNS drug targets.
Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the CNS where they control a variety of neuronal functions. Due to their roles in a number of CNS processes, mAChRs have long been a target of the drug discovery industry; however, the only mAChR ligands approved for use in the clinic are non-selective antagonists for the treatment of Parkinson's disease. This article briefly reviews recent progress made in mAChR drug discovery for Alzheimer's disease (AD), schizophrenia and Parkinson's disease, with particular emphasis on novel target validation, as well as highlighting novel indications such as drug addiction.
Langmead
Christopher J
CJ
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Avenue, Harlow, Essex, CM19 5AW, UK. christopher.j.langmead@gsk.com <christopher.j.langmead@gsk.com>
Watson
Jeannette
J
Reavill
Charlie
C
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018721:Muscarinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018727:Muscarinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000187:drug effects / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000378:metabolism; D043588:Receptor, Muscarinic M4 / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism
D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D002491:Central Nervous System Agents; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic