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
Clozapine metabolites protect dopaminergic neurons through inhibition of microglial NADPH oxidase.	2016 May 16	27184631

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 GMT 2023` Edited by `admin` on `Sat Dec 16 08:37:53 GMT 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