CLOZAPINE N-OXIDE Chemical Properties

Melting point:

190-248°C

Flash point:

9℃

storage temp. 

-20°C Freezer, Under Inert Atmosphere

solubility 

Soluble in DMSO.

form 

powder

pka

6.86±0.20(Predicted)

color 

Yellow

biological source

synthetic

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.

InChI

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

InChIKey

OGUCZBIQSYYWEF-UHFFFAOYSA-N

SMILES

N1=C(N2CC[N+]([O-])(C)CC2)C2=CC=CC=C2NC2=CC=C(Cl)C=C12

Safety Information

Hazard Codes 

Xn,T,F

Risk 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

HS Code 

29335990

MSDS

• Language:English Provider:SigmaAldrich

CLOZAPINE N-OXIDE Usage And Synthesis

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

Clozapine N-oxide has been used:

• for the activation of human M4 muscarinic (hM4Di) in primary motor cortex
• for inducing in vivo chemogenetic manipulation and impairing locomotor activity in Th-cre transgenic mice
• in behavioral testing in mice and for stimulating (HEK293) cells

Uses

A 5-HT2 antagonist. A major metabolite of clozapine that can be monitored by HPLC. Possesses little or no activity towards serotonin receptors

Definition

ChEBI: Clozapine N-oxide is a dibenzodiazepine.

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.

storage

Room temperature (desiccate)

References

[1] BIRGIT EIERMANN. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine[J]. British journal of clinical pharmacology, 2003, 44 5: 439-446. DOI:10.1046/j.1365-2125.1997.t01-1-00605.x
[2] BLAINE N ARMBRUSTER. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007: 5163-5168. DOI:10.1073/pnas.0700293104
[3] YUEJUN CHEN. Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson’s Disease.[J]. Cell stem cell, 2016, 18 6: 817-826. DOI:10.1016/j.stem.2016.03.014
[4] ELENA M VAZEY  Gary A J. Designer receptors: therapeutic adjuncts to cell replacement therapy in Parkinson’s disease.[J]. Journal of Clinical Investigation, 2014, 124 7: 2858-2860. DOI:10.1172/jci76833
[5] JUAN L. GOMEZ. Chemogenetics revealed: DREADD occupancy and activation via converted clozapine[J]. Science, 2017, 357 6350. DOI:10.1126/science.aan2475
[6] CATHERINE A. MARCINKIEWCZ. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala[J]. Nature, 2016, 537 7618: 97-101. DOI:10.1038/nature19318

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