Muscarinic Acetylcholine Receptor Antibodies

The muscarinic receptor family comprises five G protein-coupled receptor subtypes, M1 through M5, encoded by the CHRM1–CHRM5 genes and widely expressed throughout the central and peripheral nervous systems. M1, M3, and M5 primarily couple to Gq/11 proteins, activating phospholipase C signaling and increasing intracellular calcium levels, whereas M2 and M4 couple to Gi/o proteins and inhibit adenylyl cyclase activity. Together, these receptors regulate diverse physiological processes including cognition, memory, cardiac function, smooth muscle contraction, glandular secretion, and neurotransmitter release. Their expression is controlled by tissue-specific transcriptional programs, developmental cues, neuronal activity, and receptor trafficking mechanisms such as phosphorylation, desensitization, and internalization. Dysregulation of muscarinic signaling has been implicated in neurological, psychiatric, cardiovascular, respiratory, and gastrointestinal disorders. Numerous clinically approved drugs target muscarinic receptors, although most lack subtype selectivity. Examples include atropine, a non-selective antagonist used for symptomatic bradycardia, tiotropium for chronic obstructive pulmonary disease, and darifenacin for overactive bladder. More recently, xanomeline, a preferential M1/M4 agonist administered in combination with trospium, has been approved for the treatment of schizophrenia. Ongoing research focuses on developing highly selective modulators for individual M subtypes to improve therapeutic efficacy while reducing adverse effects.