U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of CLOZAPINE N-OXIDE

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
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

Curator's Comment: In monkeys, clozapine N-oxide is restricted from the CNS through active transport at the blood-brain barrier.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P04839
Gene ID: 1536.0
Gene Symbol: CYBB
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
PubMed

PubMed

TitleDatePubMed
Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro.
2004 Mar
The history of clozapine and its emergence in the US market: a review and analysis.
2007 Mar
Clozapine metabolites protect dopaminergic neurons through inhibition of microglial NADPH oxidase.
2016 May 16
Patents

Patents

Sample Use Guides

In a study of reversibility of clozapine metabolism, 100 mg of clozapine N-oxide was orally administered to schizophrenic patients.
Route of Administration: Oral
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 Thu Jul 06 14:05:01 UTC 2023
Edited
by admin
on Thu Jul 06 14:05:01 UTC 2023
Record UNII
MZA8BK588J
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Thu Jul 06 14:05:01 UTC 2023 , Edited by admin on Thu Jul 06 14:05:01 UTC 2023
PRIMARY
MESH
C079149
Created by admin on Thu Jul 06 14:05:01 UTC 2023 , Edited by admin on Thu Jul 06 14:05:01 UTC 2023
PRIMARY
WIKIPEDIA
Clozapine N-oxide
Created by admin on Thu Jul 06 14:05:01 UTC 2023 , Edited by admin on Thu Jul 06 14:05:01 UTC 2023
PRIMARY
NSC
750266
Created by admin on Thu Jul 06 14:05:01 UTC 2023 , Edited by admin on Thu Jul 06 14:05:01 UTC 2023
PRIMARY
FDA UNII
MZA8BK588J
Created by admin on Thu Jul 06 14:05:01 UTC 2023 , Edited by admin on Thu Jul 06 14:05:01 UTC 2023
PRIMARY
CAS
34233-69-7
Created by admin on Thu Jul 06 14:05:01 UTC 2023 , Edited by admin on Thu Jul 06 14:05:01 UTC 2023
PRIMARY
EPA CompTox
DTXSID50955778
Created by admin on Thu Jul 06 14:05:01 UTC 2023 , Edited by admin on Thu Jul 06 14:05:01 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> METABOLITE LESS ACTIVE
APPEARS TO HAVE LESS ACTIVITY THAN CLOZAPINE AND NORCLOZAPINE AGAINST 5HT RECEPTORS
MAJOR