Clozapine N-oxide (CNO) is a synthetic drug used mainly in biomedical research as a ligand to activate DREADD receptors. Although CNO was initially believed to be biologically inert. However, it has been shown not to enter the brain after administration and to reverse metabolise in peripheral tissues to form clozapine. Clozapine can bind to a number of different serotonergic, dopaminergic and adrenergic receptors within the brain. Therefore, behavioural data using the CNO-DREADD system in neuroscience experiments have to be interpreted with caution.
Alternatives to CNO with more affinity, more inert character, and faster kinetics include Compound 21 (C21) and deschloroclozapine (DCZ).