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Target intelligence / Profile preview
Muscarinic Acetylcholine M4 Receptor (CHRM4)
- Target
- CHRM4
- Molecular classification
- G protein-coupled receptor, GPCR, Receptor
01
Overview
The muscarinic acetylcholine receptor M4 (CHRM4) is a G protein-coupled receptor that mediates the effects of acetylcholine in the central and peripheral nervous systems. Primarily expressed in the forebrain and striatum, it acts as an inhibitory autoreceptor, regulating dopamine signaling and motor control. Its role in neurological disorders like Parkinson's disease, schizophrenia, and Alzheimer's disease makes it a potential drug target. Peripherally, it regulates erythropoiesis and is implicated in certain anemias. The orthosteric binding pocket is highly conserved, necessitating research into allosteric sites for improved drug selectivity.
- Other names
- M4 receptorCHRM4 receptor
02
Mechanism of action
Gi/o protein activation leading to inhibition of adenylate cyclase, decreased cAMP levels, and modulation of potassium channels and phosphoinositide breakdown.
03
Biological functions
Signal transductionInhibition of adenylate cyclase activityRegulation of dopamine signalingModulation of motor controlAutoreceptor activityRegulation of erythropoiesis
04
Disease associations
Parkinson's diseaseSchizophreniaAlzheimer's diseaseMyelodysplastic syndromeRefractory anemiaDrug addiction
05
Safety considerations
Highly conserved orthosteric binding pocket among muscarinic receptors requires careful design to achieve subtype selectivity.Potential for off-target effects due to the widespread distribution of muscarinic receptors.Knockout or dysfunction leads to increased locomotor activity and heightened response to drugs of abuse, potentially indicating a role in addiction and reward pathways.
06
Interacting drugs
Tiotropium
2 more in the full profile.
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