Human muscarinic acetylcholine receptor M1 (M1)

Muscarinic acetylcholine receptors (M1, M2, M3, M4, and M5) are a family of G protein-coupled receptors (GPCRs) activated by the neurotransmitter acetylcholine. Each subtype exhibits unique tissue distribution and physiological roles. M1: Mainly in central nervous system (CNS), especially cerebral cortex and hippocampus; involved in cognitive functions and memory. M2: Primarily in the heart; mediates decreased heart rate and contractility. M3: Found in smooth muscle and glandular tissue; regulates smooth muscle contraction (e.g., bronchi, bladder, gut) and glandular secretion. M4 & M5: Expressed in the CNS; thought to modulate dopamine release and participate in cognitive and neuropsychiatric functions. All five subtypes are implicated in various diseases, including neurodegenerative, psychiatric, respiratory, and cardiovascular disorders. These receptors are key drug targets—muscarinic antagonists are used to treat bradycardia, overactive bladder, and chronic obstructive pulmonary disease, while efforts are underway to develop subtype-selective drugs for CNS disorders. The high conservation of the acetylcholine-binding pocket poses a challenge for drug selectivity, driving research toward allosteric modulators.

Other names

Muscarinic acetylcholine receptor M1mAChR M1CHRM1 (gene symbol for M1)M1 receptor

Antagonists: Block acetylcholine binding, inhibit receptor activation - Agonists: Stimulate receptor, mimic acetylcholine effects - Allosteric modulators: Bind non-orthosteric site, altering response to acetylcholine