Norclozapine
Identification
- Generic Name
- Norclozapine
- DrugBank Accession Number
- DB05766
- Background
ACP-104, or N-desmethylclozapine, is the major metabolite of clozapine, and is being developed by ACADIA as a novel, stand-alone therapy for schizophrenia. It combines an atypical antipsychotic efficacy profile with the added potential benefit of enhanced cognition, thereby addressing one of the major challenges in treating schizophrenia today.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 312.797
Monoisotopic: 312.114174271 - Chemical Formula
- C17H17ClN4
- Synonyms
- Demethylclozapine
- Desmethylclozapine
- N-Desmethylclozapine
- External IDs
- ACP-104
Pharmacology
- Indication
Investigated for use/treatment in schizophrenia and schizoaffective disorders.
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- Pharmacodynamics
ACP-104 is a small molecule drug candidate we are developing as a novel therapy for schizophrenia. It is known that large amounts of ACP-104, or N-desmethylclozapine, are formed in the body after administration of clozapine. That is, clozapine is metabolized to ACP-104. We discovered that ACP-104 has a unique ability to stimulate m1 muscarinic receptors, a key muscarinic receptor. The m1 muscarinic receptors are widely known to play an important role in cognition. Since clozapine itself blocks the m1 muscarinic receptor, patients need to extensively metabolize clozapine into ACP-104 to stimulate this receptor and thereby overcome the blocking action of clozapine. Administration of ACP-104 will avoid the variability of this metabolic process and the competing action of clozapine. Like clozapine, ACP-104 is a dopamine antagonist and a 5-HT2A inverse agonist. We believe that ACP-104 represents a new approach to schizophrenia therapy that combines an atypical antipsychotic efficacy profile with the added advantage of beneficial cognitive effects.
- Mechanism of action
ACP-104 combines M1 muscarinic agonism, 5-HT2A inverse agonism, and D2 and D3 dopamine partial agonism in a single compound. ACP-104 uniquely stimulates brain cells known as M1 muscarinic receptors that play an important role in cognition. ACP-104 is a partial-agonist that causes weak activation of dopamine D2 and D3 receptors. These partial agonist properties of ACP-104 may lead to less motoric side effects than seen with most other antipsychotic drugs.
Target Actions Organism UMuscarinic acetylcholine receptor M1 Not Available Humans UDopamine D2 receptor Not Available Humans UDopamine D3 receptor Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 1I9001LWY8
- CAS number
- 6104-71-8
- InChI Key
- JNNOSTQEZICQQP-UHFFFAOYSA-N
- InChI
- 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
- IUPAC Name
- 6-chloro-10-(piperazin-1-yl)-2,9-diazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,9,12,14-heptaene
- SMILES
- ClC1=CC=C2NC3=C(C=CC=C3)C(=NC2=C1)N1CCNCC1
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0060536
- PubChem Substance
- 347910220
- ChemSpider
- 14126465
- BindingDB
- 50122054
- ChEBI
- 64050
- ChEMBL
- CHEMBL845
- ZINC
- ZINC000003995781
- Wikipedia
- Desmethylclozapine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Schizophrenia 1 1 Completed Not Available Schizophrenia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.203 mg/mL ALOGPS logP 3.25 ALOGPS logP 3.02 Chemaxon logS -3.2 ALOGPS pKa (Strongest Acidic) 15.9 Chemaxon pKa (Strongest Basic) 8.83 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 39.66 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 92.06 m3·mol-1 Chemaxon Polarizability 33.57 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 175.7209278 predictedDarkChem Lite v0.1.0 [M-H]- 165.41747 predictedDeepCCS 1.0 (2019) [M-H]- 175.7209278 predictedDarkChem Lite v0.1.0 [M-H]- 165.41747 predictedDeepCCS 1.0 (2019) [M+H]+ 176.1817278 predictedDarkChem Lite v0.1.0 [M+H]+ 167.77547 predictedDeepCCS 1.0 (2019) [M+H]+ 176.1817278 predictedDarkChem Lite v0.1.0 [M+H]+ 167.77547 predictedDeepCCS 1.0 (2019) [M+Na]+ 175.6061278 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.09746 predictedDeepCCS 1.0 (2019) [M+Na]+ 175.6061278 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.09746 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Potassium channel regulator activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name
- DRD2
- Uniprot ID
- P14416
- Uniprot Name
- D(2) dopamine receptor
- Molecular Weight
- 50618.91 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled amine receptor activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
- Gene Name
- DRD3
- Uniprot ID
- P35462
- Uniprot Name
- D(3) dopamine receptor
- Molecular Weight
- 44224.335 Da
Drug created at November 18, 2007 18:27 / Updated at March 19, 2022 06:30