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The Muscarinic Acetylcholine Receptor M5: Therapeutic Implications and Allosteric Modulation

期刊

ACS CHEMICAL NEUROSCIENCE
卷 10, 期 3, 页码 1025-1034

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.8b00481

关键词

M-5; muscarinic; allosteric modulator; knockout; Alzheimer's disease; schizophrenia; addiction

资金

  1. NIDA [DA037207]
  2. William K. Warren Foundation

向作者/读者索取更多资源

The muscarinic acetylcholine receptor (mAChR) subtype 5 (M-5) was the most recent mAChR to be cloned and has since emerged as a potential therapeutic target for a number of indications. Early studies with knockout animals have provided clues to the receptor's role in physiological processes related to Alzheimer's disease, schizophrenia, and addiction, and until recently, useful subtype-selective tools to further probe the pharmacology of M-5 have remained elusive. Small-molecule allosteric modulators have since gained traction as a means by which to selectively examine muscarinic pharmacology. This review highlights the discovery and optimization of M-5 positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs).

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