Muscarinic acetylcholine receptor M2 and M4 (M2/M4 receptors)

Muscarinic acetylcholine receptors M2 and M4 are G protein-coupled receptors (GPCRs) that primarily signal through the Gi/o inhibitory pathway, leading to the inhibition of adenylate cyclase and a decrease in intracellular cyclic AMP (cAMP). The M2 receptor is widely expressed in the heart, where it mediates the parasympathetic slowing of heart rate, and in smooth muscle, while the M4 receptor is predominantly localized in the central nervous system, particularly in the striatum and cortex. In the brain, these receptors function as inhibitory autoreceptors and heteroreceptors that modulate the release of various neurotransmitters, including acetylcholine and dopamine. This regulatory role makes them critical targets for treating neuropsychiatric and neurological disorders; for instance, M4 agonists are a novel class of antipsychotics (e.g., KarXT) that reduce hyperdopaminergic activity in schizophrenia without the motor side effects of traditional D2 antagonists. Additionally, M2 and M4 receptors are involved in cognitive processes and motor control, and their dysfunction is implicated in Alzheimer's and Parkinson's diseases.

Other names

CHRM2CHRM4Muscarinic acetylcholine receptor 2Muscarinic acetylcholine receptor 4HM2HM4M2RM4R

Agonism (to reduce dopamine release in schizophrenia), Antagonism (to prevent smooth muscle contraction in COPD or overactive bladder)