Designer muscarinic acetylcholine receptor (DREADD (for Designer Receptors Exclusively Activated by Designer Drug))

Designer muscarinic receptors are genetically engineered variants of muscarinic acetylcholine receptors (mAChRs), usually based on the human M3 or M4 subtypes, that have been modified to be unresponsive to acetylcholine but selectively activated by otherwise inert synthetic ligands such as clozapine-N-oxide (CNO)[1]. These engineered GPCRs, commonly known as DREADDs, allow precise spatiotemporal control of cell signaling in experimental systems, especially in neuroscience research for manipulating specific neural circuits in animal models. While not endogenous therapeutic targets, they represent a central tool ("chemogenetics") in modern functional studies to dissect physiological or pathological pathways and test circuit-based interventions in preclinical disease models[1].

Other names

DREADDdesigner receptorengineered muscarinic receptorCNO-sensitive muscarinic receptor

Synthetic ligand-induced activation or inhibition of engineered GPCRs, controlling downstream signaling pathways (e.g., Gq, Gi/o, Gs pathways depending on receptor design)