Clozapine N-oxide (CNO) is a synthetic drug used mainly in biomedical research as a ligand to activate Designer Receptors Exclusively Activated by Designer Drugs (DREADDs),[1] despite the initial belief that it was biologically inert.

However, it has been shown to not enter the brain after administration[2] and to reverse metabolize in peripheral tissues to form clozapine.

Clozapine can bind to a number of different serotonergic, dopaminergic and adrenergic receptors within the brain.

[3] These off-target effects mean behavioral data using the CNO-DREADD system have to be interpreted with caution.

[4] Alternatives to CNO with more affinity, more inert character, and faster kinetics include Compound 21 (C21)[5] and deschloroclozapine (DCZ).