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Scientific media resources
Muscarinic acetylcholine receptors

Muscarinic acetylcholine receptors (mAChRs) are a subfamily of G protein-coupled receptors that regulate numerous fundamental functions of the central and peripheral nervous systems. There are 5 subtypes1 :
 

Receptors

Muscarinic receptors are distributed throughout many areas of the body and are responsible for various activities based on location and receptor subtype, including2-4:
 

  • Neuronal activation and signaling
  • Behavior, learning and memory
  • Cardiac function
  • Smooth muscle function
  • Function of glands involved in saliva and insulin production

The activation of muscarinic receptors results in either an increase or decrease in signaling within the cell depending on the receptor subtype3:
 

Activation results in:
 

Receptors activity


The role of M1 & M4 receptors in neurological disease

M1 and M4 receptors are present in the central nervous system (CNS) and are localized in brain regions responsible for a variety of functions, including behavior and cognition.3,5

Image features two illustrations of the human brain, highlighting specific brain regions in green and purple. The text emphasizes the importance of muscarinic receptors and their potential impact on treating neuropsychiatric conditions.

Certain behavioral and cognitive symptoms of neuropsychiatric diseases may be caused by impairments of brain circuits that impact and can be modulated by M1 and M4 receptor activity and/or expression as well as acetylcholine, the neurotransmitter and molecule that binds to mAChRs. 
 

  • Acetylcholine is released in the brain and binds to the M1 and M4 receptors to help regulate neurological function. 
  • M1 and M4 receptors are located in areas of the brain thought to be associated with behavioral and cognitive symptoms. 
  • Abnormal activity of M1 and M4 receptors in these areas of the brain may exacerbate those symptoms.6

Research implications

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Research suggests that M1 and M4 receptors may play a key role in neuronal signaling in brain regions that are thought to be implicated in a variety of neuropsychiatric conditions, including6,7:

  • Schizophrenia
  • Alzheimer’s disease-associated cognitive impairment, psychosis and agitation 
  • Bipolar I disorder 
  • Irritability associated with autism

Bristol Myers Squibb is committed to rapidly advancing an innovative and diverse pipeline in neuroscience. We are researching key pathways to slow or stop disease progression and treat symptoms to achieve the greatest possible outcomes for patients.
 

References

  1. Kruse AC, Kobilka BK, Gautam D, Sexton PM, Christopoulos A, Wess J. Muscarinic acetylcholine receptors: novel opportunities for drug development. Nat Rev Drug Discov. 2014;13(7):549-560. 
  2. Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol. 2006;148(5):565-578. 
  3. Kudlak M, Tadi P. Physiology, Muscarinic Receptor. PubMed. Last Updated August 8, 2023. Accessed October 29, 2024. https://www.ncbi.nlm.nih.gov/books/NBK555909/
  4. Paul SM, Yohn SE, Popiolek M, Miller AC, Felder CC. Muscarinic Acetylcholine Receptor Agonists as Novel Treatments for Schizophrenia. Am J Psychiatry. 2022;179(9). 
  5. Fu L, Luo Y, Niu L, et al. M1/M4 receptors as potential therapeutic treatments for schizophrenia: A comprehensive study. Bioorg Med Chem. 2024;105:117728. 
  6. Dwomoh L, Tejeda GS, Tobin AB. Targeting the M1 muscarinic acetylcholine receptor in Alzheimer’s disease. Neuronal signaling. 2022;6(1): NS20210004. 
  7. Erskine D, Taylor JP, Bakker G, Brown AJH, Tasker T, Nathan PJ. Cholinergic muscarinic M1 and M4 receptors as therapeutic targets for cognitive, behavioural, and psychological symptoms in psychiatric and neurological disorders.
    Drug Discov Today. 2019;24(12):2307-2314