Human muscarinic designer receptors (DREADDs)

Clozapine N-oxide (CNO) can bind to non-DREADD receptors at concentrations required for DREADD activation, and undergoes reverse-metabolism to its parent compound clozapine, an atypical antipsychotic that acts at a variety of pharmacological targets and produces numerous physiological and behavioral effects.

After a single intraperitoneal (i.p.) injection of Clozapine N-oxide (1 mg/kg) into mice, Clozapine N-oxide (CNO) plasma levels peak at 15 min and are very low after 2 h. Despite the short plasma half-life of CNO in mice, the biological effects that have been described after acute treatment of DREADD-expressing experimental animals are usually much longer (6-10 h).