Cholinergic receptor muscarinic 4 (CHRM4 (often abbreviated as M4 or M4R in the literature))

Cholinergic receptor muscarinic 4 (CHRM4 or M4R) is a subtype of muscarinic acetylcholine receptor that belongs to the G protein-coupled receptor family. It mediates cellular responses to the neurotransmitter acetylcholine mainly by coupling to Gi/o proteins, leading to inhibition of adenylate cyclase and decreased cAMP production. M4 receptors are widely expressed in the brain, particularly in the striatum and forebrain, where they are involved in the regulation of dopamine signaling, synaptic plasticity, and feedback inhibition of neurotransmitter release. Functionally, the M4 receptor plays important roles in learning, memory, motor control, and behavioral responses to drugs of abuse. Dysregulation of M4 signaling has been implicated in the pathophysiology of schizophrenia, movement disorders such as Parkinson’s disease, and cognitive impairment in neurodegenerative diseases like Alzheimer’s. M4 is a validated therapeutic target, with several orthosteric and allosteric modulators being developed to treat CNS disorders with improved selectivity and safety relative to nonselective muscarinic agents[1][2][3][4][5][6].

Other names

Muscarinic acetylcholine receptor M4M4 muscarinic receptorM4RCHRM4

Agonists: Activate G protein-coupled signaling (primarily Gi/o-mediated inhibition of adenylate cyclase). Allosteric modulators: Bind to less-conserved allosteric sites, enhancing or modulating agonist responses. Antagonists: Block acetylcholine binding or receptor activation, inhibiting downstream signaling. Dual actions (orthosteric and allosteric coupling).