Human muscarinic acetylcholine receptor M4 (DREADD mutated) (CHRM4 DREADD)

The **Human muscarinic acetylcholine receptor M4 DREADD** is an engineered version of the human muscarinic acetylcholine receptor M4 (CHRM4), part of the G protein-coupled receptor family, modified for chemogenetic research. The DREADD (Designer Receptor Exclusively Activated by Designer Drugs) mutation disables native activation by acetylcholine and enables selective activation by synthetic ligands, typically clozapine-N-oxide (CNO). Naturally, M4 receptors function as Gi/o-coupled inhibitory autoreceptors, modulating acetylcholine and dopamine release in the central nervous system, influencing movement, cognition, and neuropsychiatric disorders[1][2][5]. The DREADD technology is a powerful research tool for selectively controlling neuron populations in vivo, but it is not a native physiological target or a therapeutic molecule itself and requires exogenous gene expression. The term "M4 DREADD" refers specifically to the mutated receptor, not the wild-type, and its clinical utility is confined to research applications due to concerns about selectivity and safety.

Other names

Muscarinic acetylcholine receptor M4 DREADDhM4Diengineered human muscarinic receptor M4 DREADDDesigner Receptor Exclusively Activated by Designer Drugs M4

(DREADD system) Activation by synthetic ligand CNO (not activated by acetylcholine) triggers Gi/o signaling, inhibiting adenylyl cyclase and reducing cAMP levels, leading to inhibition of neuronal activity.\n(Native) Activation by acetylcholine or selective agonist leads to coupling to Gi/o proteins, inhibiting neurotransmission[1][2].