Histamine H1 and muscarinic acetylcholine receptors M1–M5 (H1/mAChR (M1–M5))

The H1 and muscarinic M1–M5 receptors target profile refers to the simultaneous modulation of the histamine H1 receptor and the five subtypes of muscarinic acetylcholine receptors (M1, M2, M3, M4, and M5). These receptors are all members of the G protein-coupled receptor (GPCR) superfamily and are widely distributed throughout the central and peripheral nervous systems, where they regulate processes such as arousal, smooth muscle tone, and cognition. This specific polypharmacological profile is a hallmark of several atypical antipsychotics and first-generation antihistamines. While H1 antagonism contributes to the sedative and anti-emetic properties of these drugs, it is also linked to metabolic side effects like weight gain. Muscarinic antagonism can mitigate extrapyramidal side effects in antipsychotic therapy but frequently causes dose-limiting peripheral effects such as dry mouth and constipation, as well as central cognitive impairment.

Other names

H1 and M1–M5 receptorsHistamine H1 and muscarinic receptorsH1/mAChR (M1–M5)Histamine H1 and muscarinic acetylcholine receptors

Antagonism or inverse agonism of the histamine H1 receptor and muscarinic acetylcholine receptor subtypes M1, M2, M3, M4, and M5.