34233-69-7

Basic information

• Product Name: CLOZAPINE N-OXIDE
• Synonyms: e)(1,4)diazepine,8-chloro-11-(4-methyl-1-piperazinyl)-5h-dibenzo(n-oxide;CLOZAPINE N-OXIDE;8-CHLORO-11-[4-METHYL-1-PIPERAZINYL]-5H-DIBENZO[B,E][1,4]DIAZEPINE N-OXIDE;Clozapine N-oxide solution;Clozapine N-oxide Methanol Adduct;Clozapine Impurity 8
• CAS NO: 34233-69-7
• Molecular Formula: C18H19ClN4O
• Molecular Weight: 342.82
• Product Categories: Various Metabolites and Impurities;Metabolites
• Mol File: 34233-69-7.mol
• Article Data: 0

Chemical Properties

• Melting Point: 190-248°C
• Boiling Point: 517.4°Cat760mmHg
• Flash Point: 9℃
• Appearance: /
• Density: 1.36g/cm³
• Vapor Pressure: 1.57E-11mmHg at 25°C
• Refractive Index: 1.685
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Soluble in DMSO.
• PKA: 6.86±0.20(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: CLOZAPINE N-OXIDE(CAS DataBase Reference)
• NIST Chemistry Reference: CLOZAPINE N-OXIDE(34233-69-7)
• EPA Substance Registry System: CLOZAPINE N-OXIDE(34233-69-7)

Safety Data

• Hazard Codes: Xn,T,F
• Statements: 22-36/37/38-39/23/24/25-23/24/25-11
• Safety Statements: 26-36-45-36/37-16-7
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: HP1760000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 34233-69-7(Hazardous Substances Data)

Usage

Description

Clozapine-N-oxide (34233-69-7) is a clozapine?metabolite1?which is pharmacologically inert2. Agonist at human muscarinic designer receptors known as DREADDs, (designer receptors exclusively activated by designer drug).2?May be used to control grafted human pluripotent stem cell-derived neurons engineered to express DREADDs.3,4??Numerous other applications.5,6

Chemical Properties

Yellow Solid

Uses

Different sources of media describe the Uses of 34233-69-7 differently. You can refer to the following data:
1. Clozapine N-oxide has been used:for the activation of human M4 muscarinic (hM4Di) in primary motor cortexfor inducing in vivo chemogenetic manipulation and impairing locomotor activity in Th-cre transgenic micein behavioral testing in mice and for stimulating (HEK293) cells
2. A 5-HT2 antagonist. A major metabolite of clozapine that can be monitored by HPLC. Possesses little or no activity towards serotonin receptors

General Description

Clozapine N-oxide (CNO), inactive from of clozapine drug, activates G-protein-coupled receptors (GPCRs). CNO serves as a synthetic ligand for engineered human muscarinic receptor. It elicits clozapine-like effects upon metabolic conversion. Clozapine conversion to CNO favors its passage through blood-brain barrier.

Biochem/physiol Actions

5-HT2 serotonin receptor antagonist; major metabolite of clopazine that can be monitored by HPLC.

References

1) Eiermann?et al.?(1997),?The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine; Br. J. Clin. Pharmacol.,?44?439 2) Armbruster?et al.?(2007),?Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand; Proc. Natl. Acad. Sci. USA,?104?5163 3) Chen?et al.?(2016),?Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson’s Disease; Cell Stem Cell,?18?817 4) Vazey and Aston-Jones (2014),?Designer receptors: therapeutic adjuncts to cell replacement therapy in Parkinson’s disease: J. Clin. Invest.,?124?2858 5) Gomez?et al.?(2017)?Chemogenetics revealed: DREADD occupancy and activation via converted clozapine; Science?357?503 6) Marcinkiewcz?et al. (2016)?Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala; Nature?537?97

InChI:InChI=1/C18H19ClN4O/c1-21-8-10-22(11-9-21)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)23(18)24/h2-7,12,24H,8-11H2,1H3