Clozapine N-oxide (dihydrochloride)

2250025-93-3

415.74

H2O : 100 mg/mL (240.53 mM; Need ultrasonic); DMSO : 240 mg/mL (577.28 mM; Need ultrasonic)

GPCR/G Protein; Neuronal Signaling; Neuronal Signaling; GPCR/G Protein; Metabolic Enzyme/Protease

Clozapine N-oxide dihydrochloride is a major metabolite of Clozapine and a human muscarinic designer receptors (DREADDs) agonist. Clozapine N-oxide dihydrochloride activates the DREADD receptor hM3Dq and hM4Di. Clozapine N-oxide dihydrochloride can cross the blood-brain barrier^[1][2][3][4]. Clozapine is a potent dopamine antagonist and also a potent and selective muscarinic M4 receptor (EC₅₀=11 nM) agonist^[5][6]. IC50 & Target: Human muscarinic designer receptors (DREADDs)^[1] In Vitro: 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^[2]. In Vivo: 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)^[1].