Muscarinic acetylcholine receptor (mAChR) (mAChR)

Muscarinic acetylcholine receptors (mAChRs) are a family of five G protein-coupled receptors (M1–M5) that mediate the metabotropic actions of acetylcholine in both the central and peripheral nervous systems [1][2]. These receptors play a fundamental role in regulating parasympathetic functions, such as heart rate, smooth muscle contraction, and glandular secretions, as well as complex cognitive processes like learning and memory [1][3]. In clinical practice, mAChRs are significant therapeutic targets for a variety of conditions; for example, M3 antagonists are used to treat chronic obstructive pulmonary disease (COPD) and overactive bladder, while M1 and M4 receptors are targets for novel treatments in Alzheimer's disease and schizophrenia [4][5]. However, the broad expression of these receptors across multiple organ systems often leads to dose-limiting side effects, including dry mouth, constipation, and cognitive impairment [6][9]. Consequently, current research focuses on developing subtype-selective ligands and allosteric modulators to achieve better therapeutic precision and safety profiles [3][5].

Other names

Cholinergic muscarinic receptorMuscarinic receptorCHRMmAChRs

Muscarinic receptors are G protein-coupled receptors (GPCRs) that signal through either Gq/11 (M1, M3, M5) to activate phospholipase C and increase intracellular calcium, or Gi/o (M2, M4) to inhibit adenylyl cyclase and decrease cAMP levels [1][2]. Drugs targeting these receptors function as orthosteric agonists, which mimic acetylcholine, or antagonists, which competitively block acetylcholine binding, thereby modulating parasympathetic and central nervous system activity [5].