CLOZAPINE N-OXIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H19ClN4O
Molecular Weight	342.823
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[N+]1([O-])CCN(CC1)C2=NC3=C(NC4=C2C=CC=C4)C=CC(Cl)=C3

InChI

InChIKey=OGUCZBIQSYYWEF-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C18H19ClN4O
Molecular Weight	342.823
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9384460
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17360345 | https://www.ncbi.nlm.nih.gov/pubmed/27184631 | https://www.ncbi.nlm.nih.gov/pubmed/27822508

Clozapine N-oxide is a phase 1 metabolite of antipsychotic drug clozapine, produced by oxidation of clozapine by CYP3A4. Clozapine N-oxide is inert with respect to a wide range of GPCRs. It was used a tool compound in the DREADD (designer receptors exclusively activated by designer drugs) system in which a mutated muscarinic G protein-coupled receptor is activated by an otherwise inert compound, however interpretation of experiments is confounded by the ability of clozapine-N-oxide to convert to clozapine upon administration. Clozapine N-oxide exhibits neuroprotective action by inhibiting of microglial NADPH oxidase.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome b-245 heavy chain 5 Target ID: P04839 Gene ID: 1536.0 Gene Symbol: CYBB Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27184631	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro.	2004 Mar	14751426
The history of clozapine and its emergence in the US market: a review and analysis.	2007 Mar	17580753

Patents

Sample Use Guides

In Vivo Use Guide

In a study of reversibility of clozapine metabolism, 100 mg of clozapine N-oxide was orally administered to schizophrenic patients.

Route of Administration: Oral

In Vitro Use Guide

To investigate neuroprotective effects of clozapine N-oxide (CNO), the in vitro model of inflammation elicited neurotoxicity was used. Neuron-glia cultures with Escherichia coliendotoxin LPS, and dopamine uptake capacity and cell counts of THir neurons were performed to determine the function and survival of DA neurons 7 days after LPS treatment. Pretreatment with CNO protected DA neurons against an LPS-induced reduction of uptake capacity in a bell-shaped curve with a maximal effect achieved at 0.1 uM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:37:53 UTC 2023` Edited by `admin` on `Sat Dec 16 08:37:53 UTC 2023`
Record UNII	MZA8BK588J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CLOZAPINE N-OXIDE

Common Name

English

8-CHLORO-11-(4-METHYL-1-PIPERAZINYL)-5H-DIBENZO(B,E)(1,4)DIAZEPINE N-OXIDE

Systematic Name

English

5H-DIBENZO(B,E)(1,4)DIAZEPINE, 8-CHLORO-11-(4-METHYL-4-OXIDO-1-PIPERAZINYL)-

Systematic Name

English

NSC-750266

Code

English

Code System Code Type Description

PUBCHEM

135445691