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

Details

Stereochemistry ACHIRAL
Molecular Formula C17H17ClN4
Molecular Weight 312.797
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORCLOZAPINE

SMILES

ClC1=CC2=C(NC3=C(C=CC=C3)C(=N2)N4CCNCC4)C=C1

InChI

InChIKey=JNNOSTQEZICQQP-UHFFFAOYSA-N
InChI=1S/C17H17ClN4/c18-12-5-6-15-16(11-12)21-17(22-9-7-19-8-10-22)13-3-1-2-4-14(13)20-15/h1-6,11,19-20H,7-10H2

HIDE SMILES / InChI

Molecular Formula C17H17ClN4
Molecular Weight 312.797
Charge 0
Count
Stereochemistry ACHIRAL
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 http://news.acadia-pharm.com/phoenix.zhtml?c=125180&p=irol-newsArticle&ID=1166151

ACP-104 or N-Desmethylclozapine (NDMC), or norclozapine is a major metabolite of clozapine, which was developed like a small molecule drug candidate by ACADIA for treatment schizophrenia. ACP-104 combines M1 muscarinic agonist, 5-HT2A inverse agonist, and D2 and D3 dopamine partial agonist in a single compound and, therefore, uniquely addresses what ACADIA believed are the three most promising target mechanisms for treating schizophrenia. Then drug was discontinued, because the study did not meet its primary endpoint of antipsychotic efficacy or any of the secondary endpoints. Neither dose of ACP-104 demonstrated improved efficacy as compared to placebo. The most common adverse events in the treatment arms relative to placebo were increased salivation, tachycardia, and dyspepsia, which were noted to be dose-related. There was no clinically significant decrease in neutrophil counts in the study drug arms.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1.
1997 May 3
Tertiary N-glucuronides of clozapine and its metabolite desmethylclozapine in patient urine.
2001 Oct
Central effects of clozapine in regulating micturition in anesthetized rats.
2002
Differing response to antipsychotic therapy in schizophrenia: pharmacogenomic aspects.
2004 Mar
Increased serum interleukin-1beta and interleukin-6 in elderly, chronic schizophrenic patients on stable antipsychotic medication.
2005 Jun
Dopamine uptake inhibitor-induced rotation in 6-hydroxydopamine-lesioned rats involves both D1 and D2 receptors but is modulated through 5-hydroxytryptamine and noradrenaline receptors.
2005 Mar
High throughput therapeutic drug monitoring of clozapine and metabolites in serum by on-line coupling of solid phase extraction with liquid chromatography-mass spectrometry.
2006 Apr 13
Structural requirements of transmembrane domain 3 for activation by the M1 muscarinic receptor agonists AC-42, AC-260584, clozapine, and N-desmethylclozapine: evidence for three distinct modes of receptor activation.
2006 Dec
Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs.
2006 Oct 20
Bioequivalence of clozapine orally disintegrating 100-mg tablets compared with clozapine solid oral 100-mg tablets after multiple doses in patients with schizophrenia.
2008
Patents

Patents

Sample Use Guides

Patients recieved single low or high dose of ACP-104 (NORCLOZAPINE): 25mg, 75mg, 125mg, 175mg, 225mg, or 275mg once a day for 2 weeks or 50mg, 100mg, 150mg, 200mg, 250mg, or 300mg daily for 2 weeks
Route of Administration: Oral
It was determined the effects of clozapine (Cloz) and its metabolites norclozapine (Norcloz) on the 5-HT(2) receptor system on the levels of protein and gene expression in in vitro systems of primary cortical cells of the rat and human hippocampal SHS5Y5 neuroblastoma cells. A significant decrease was found in primary cortical cells for 5-HT(2) receptor density (Cloz 200/Cloz 400/Norcloz 200. 5-HT(2A) receptor mRNA levels were also significantly reduced (Norcloz 200 vs. control) in SHS5Y5 cells. GAPDH mRNA levels were not affected.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:50:07 GMT 2023
Edited
by admin
on Fri Dec 15 15:50:07 GMT 2023
Record UNII
1I9001LWY8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NORCLOZAPINE
Common Name English
CLOZAPINE IMPURITY C [USP IMPURITY]
Common Name English
NDMC
Common Name English
N-DESMETHYLCLOZAPINE
Common Name English
DESMETHYLCLOZAPINE
Common Name English
8-CHLORO-11-PIPERAZIN-1-YL-5H-DIBENZO(B,E)(1,4)DIAZEPINE
Systematic Name English
Code System Code Type Description
SMS_ID
100000174142
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
CHEBI
64050
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
DRUG BANK
DB05766
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
PUBCHEM
135409468
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
WIKIPEDIA
DESMETHYLCLOZAPINE
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
FDA UNII
1I9001LWY8
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
CAS
6104-71-8
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
EPA CompTox
DTXSID0042616
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
MESH
C058272
Created by admin on Fri Dec 15 15:50:07 GMT 2023 , Edited by admin on Fri Dec 15 15:50:07 GMT 2023
PRIMARY
Related Record Type Details
BINDER->LIGAND
Related Record Type Details
PARENT -> METABOLITE ACTIVE
ACTIVITY OF NORCLOZAPINE AGAINST DOPAMINE AND SEROTONIN RECEPTOR MAY DIFFER FROM THAT OF CLOZAPINE
MAJOR
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY