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Details

Stereochemistry ACHIRAL
Molecular Formula C17H17ClN4
Molecular Weight 312.7973
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORCLOZAPINE

SMILES

c1ccc2c(c1)C(=Nc3cc(ccc3N2)Cl)N4CCNCC4

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 312.7973
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
Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine.
1995 Feb
Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1.
1997 May 3
Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia.
2000 Nov
Lack of CYP3A4 inhibition by grapefruit juice and ketoconazole upon clozapine administration in vivo.
2001
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
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
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
N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity.
2003 Nov 11
Differing response to antipsychotic therapy in schizophrenia: pharmacogenomic aspects.
2004 Mar
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 S100B in elderly, chronic schizophrenic patients: negative correlation with deficit symptoms.
2005 Dec 15
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
An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels.
2005 May
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
Massively parallel screening of the receptorome.
2008 Jul
Effect of food on the pharmacokinetics of clozapine orally disintegrating tablet 12.5 mg: a randomized, open-label, crossover study in healthy male subjects.
2009
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 Sat Jun 26 10:17:51 UTC 2021
Edited
by admin
on Sat Jun 26 10:17:51 UTC 2021
Record UNII
1I9001LWY8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NORCLOZAPINE
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
CLOZAPINE IMPURITY C [USP]
Common Name English
Code System Code Type Description
DRUG BANK
DB05766
Created by admin on Sat Jun 26 10:17:51 UTC 2021 , Edited by admin on Sat Jun 26 10:17:51 UTC 2021
PRIMARY
PUBCHEM
135409468
Created by admin on Sat Jun 26 10:17:51 UTC 2021 , Edited by admin on Sat Jun 26 10:17:51 UTC 2021
PRIMARY
WIKIPEDIA
DESMETHYLCLOZAPINE
Created by admin on Sat Jun 26 10:17:51 UTC 2021 , Edited by admin on Sat Jun 26 10:17:51 UTC 2021
PRIMARY
FDA UNII
1I9001LWY8
Created by admin on Sat Jun 26 10:17:51 UTC 2021 , Edited by admin on Sat Jun 26 10:17:51 UTC 2021
PRIMARY
CAS
6104-71-8
Created by admin on Sat Jun 26 10:17:51 UTC 2021 , Edited by admin on Sat Jun 26 10:17:51 UTC 2021
PRIMARY
EPA CompTox
6104-71-8
Created by admin on Sat Jun 26 10:17:51 UTC 2021 , Edited by admin on Sat Jun 26 10:17:51 UTC 2021
PRIMARY
MESH
C058272
Created by admin on Sat Jun 26 10:17:51 UTC 2021 , Edited by admin on Sat Jun 26 10:17:51 UTC 2021
PRIMARY
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BINDER->LIGAND
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PARENT -> METABOLITE ACTIVE
ACTIVITY OF NORCLOZAPINE AGAINST DOPAMINE AND SEROTONIN RECEPTOR MAY DIFFER FROM THAT OF CLOZAPINE
MAJOR
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PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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ACTIVE MOIETY