Clozapine N-oxide is a major metabolite of clozapine noted to decrease SR-2A(5-HT2 serotonin receptor) density in vitro.
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Clozapine N-oxide, a primary metabolite of Clozapine, serves as an agonist for human muscarinic designer receptors (DREADDs), effectively activating DREADD receptors hM3Dq and hM4Di, and is capable of crossing the blood-brain barrier[1].[2].[3].[4]. Clozapine itself is known as a powerful antagonist of dopamine and a selective agonist for the muscarinic M4 receptor, with an EC50 value of 11 nM[5].[6].
体内研究
After a single intraperitoneal injection of 1 mg/kg Clozapine N-oxide into mice, peak plasma levels of CNO are reached at 15 minutes, declining significantly after 2 hours. Despite this short plasma half-life in mice, the physiological and behavioral effects described following acute treatment in DREADD-expressing experimental animals typically extend much longer, between 6-10 hours[1].
体外研究
Clozapine N-oxide (CNO) can bind to non-DREADD receptors at concentrations necessary for DREADD activation and can undergo reverse metabolism back to its parent compound clozapine, an atypical antipsychotic with a wide range of pharmacological targets and effects[2].
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