Muscarinic acetylcholine receptor M1 (CHRM1) and Muscarinic acetylcholine receptor M4 (CHRM4) (M1 and M4 mAChR)

Muscarinic acetylcholine receptors are a family of G protein-coupled receptors mediating the actions of the neurotransmitter acetylcholine throughout the central and peripheral nervous systems. The M1 subtype is highly expressed in brain regions involved in cognition such as cortex and hippocampus; it plays a critical role in modulating synaptic plasticity and cognitive processes like learning and memory. The M4 subtype is also abundant in brain areas including striatum where it regulates dopaminergic neurotransmission and motor control by acting primarily via inhibitory G proteins. Both M1 and M4 have emerged as important drug targets due to their involvement in neurodegenerative diseases like Alzheimer’s disease—as potential pro-cognitive targets—and neuropsychiatric conditions like schizophrenia—as potential antipsychotic targets without some liabilities associated with dopamine antagonism. Recent advances focus on developing selective orthosteric agonists/allosteric modulators that can activate these subtypes while minimizing off-target effects mediated by other muscarinic receptors. Structural studies have revealed differences between their ligand-binding pockets that inform ongoing drug discovery efforts. In summary, "Acetylcholine muscarinic receptor M1/M4" refers collectively—but imprecisely—to two closely related yet distinct GPCRs each encoded by separate genes (CHRM1, CHRM4) with overlapping but not identical roles in CNS function and therapeutic relevance across several major neurological diseases.

Other names

CHRM1 (for Muscarinic acetylcholine receptor M1)CHRM4 (for Muscarinic acetylcholine receptor M4)mAChR-M1mAChR-M4Cholinergic receptor, muscarinic 1Cholinergic receptor, muscarinic 4

Drugs targeting these receptors act as either orthosteric agonists/antagonists or allosteric modulators. Orthosteric ligands bind to the same site as endogenous acetylcholine. Allosteric modulators bind to distinct sites to enhance or inhibit the effect of endogenous ligand binding. Positive allosteric modulators can selectively enhance signaling through specific subtypes such as M1 or M4 without activating other subtypes that may cause side effects.