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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

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
Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine.
2001 Dec 27
Tertiary N-glucuronides of clozapine and its metabolite desmethylclozapine in patient urine.
2001 Oct
Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake.
2003 May
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
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
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.
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
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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
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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
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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
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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
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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
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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
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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
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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
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