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
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
DescriptionCurator's Comment: description was created based on several sources, including
http://news.acadia-pharm.com/phoenix.zhtml?c=125180&p=irol-newsArticle&ID=1166151
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.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15900318 |
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Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16135699 |
89.0 nM [IC50] | ||
Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16135699 |
14.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Plasma clozapine levels and the treatment of L-DOPA-induced psychosis in Parkinson's disease. A high potency effect of clozapine. | 1995 Feb |
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Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1. | 1997 May 3 |
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Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine. | 2001 Dec 27 |
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Tertiary N-glucuronides of clozapine and its metabolite desmethylclozapine in patient urine. | 2001 Oct |
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Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. | 2003 May |
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Differing response to antipsychotic therapy in schizophrenia: pharmacogenomic aspects. | 2004 Mar |
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Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro. | 2004 Mar |
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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
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00628420
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14751426
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.
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100000174142
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64050
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DB05766
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135409468
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DESMETHYLCLOZAPINE
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1I9001LWY8
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6104-71-8
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DTXSID0042616
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C058272
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ACTIVE MOIETY
PARENT (METABOLITE ACTIVE)