clozapine N-oxide

Clozapine N-oxide is a synthetic compound and a major metabolite of the antipsychotic drug clozapine, formed by CYP3A4-mediated oxidation. It is best known as the canonical ligand for activating Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)—mutated muscarinic G protein-coupled receptors extensively used in neuroscience to control neural activity in vivo. Initially considered pharmacologically inert, CNO is now recognized to have limited off-target activity at standard experimental doses but can be reverse-metabolized to clozapine in vivo, especially in rodents and non-human primates, complicating interpretation of certain studies. CNO does not exhibit clinically relevant pharmacologic activity in humans at doses typically used in research. It has also been reported to inhibit microglial NADPH oxidase and may have neuroprotective effects in some in vitro models[1][2][5][6][7][9].

Other names

clozapine N-oxideCNO