Muscarinic acetylcholine receptors M1, M4, and M5 (mAChR M1/M4/M5)

Muscarinic acetylcholine receptors M1, M4, and M5 are a subset of the five muscarinic receptor subtypes (M1-M5) that belong to the G protein-coupled receptor (GPCR) family (Wikipedia, 2024). These receptors are predominantly expressed in the central nervous system, where they regulate vital functions such as cognition, memory, and the modulation of dopaminergic and glutamatergic neurotransmission (MDPI, 2025). M1 and M4 receptors are particularly concentrated in the cerebral cortex, hippocampus, and striatum, making them primary targets for treating the cognitive and psychotic symptoms of schizophrenia and Alzheimer's disease (BMS, 2025). M5 receptors, though less abundant, are uniquely localized on dopamine neurons in the ventral tegmental area and are involved in reward pathways and cerebrovascular regulation (BioRxiv, 2021). Therapeutic strategies often involve the use of agonists or positive allosteric modulators to enhance cholinergic signaling, frequently paired with peripheral antagonists to mitigate systemic side effects like nausea and salivation (NIH, 2025). Recent clinical successes, such as the FDA approval of the xanomeline-trospium combination (Cobenfy), highlight the importance of these receptors as non-dopaminergic alternatives for managing neuropsychiatric conditions (Wikipedia, 2024).

Other names

CHRM1CHRM4CHRM5Muscarinic receptor subtypes 1, 4, and 5M1, M4, and M5 muscarinic receptorsCholinergic receptor muscarinic 1, 4, and 5

Agonism of M1 and M4 receptors to modulate dopaminergic and glutamatergic signaling; positive allosteric modulation (PAM) to enhance endogenous signaling; negative allosteric modulation (NAM) for specific subtypes like M5 to reduce reward-seeking behavior (NIH, 2025; UGA, 2021).