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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
Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia.
2000 Nov
Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine.
2001 Dec 27
Isolation and identification of clozapine metabolites in patient urine.
2001 Jun
Rapid capillary electrophoretic method for the determination of clozapine and desmethylclozapine in human plasma.
2001 May 4
Correlation of antipsychotic and prolactin concentrations in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine.
2002 Summer
Pharmacokinetics of clozapine and its metabolites in hippocampal HT22 cells.
2003 Aug 29
Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake.
2003 May
Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro.
2004 Mar
Field-amplified sample stacking in capillary electrophoresis for the determination of clozapine, clozapine N-oxide, and desmethylclozapine in schizophrenics' plasma.
2004 Sep 25
Increased serum interleukin-1beta and interleukin-6 in elderly, chronic schizophrenic patients on stable antipsychotic medication.
2005 Jun
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
Massively parallel screening of the receptorome.
2008 Jul
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