This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

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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Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
UMuscarinic acetylcholine receptor M1Not AvailableHumans
UDopamine D2 receptorNot AvailableHumans
UDopamine D3 receptorNot AvailableHumans
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
Human Metabolome Database
HMDB0060536
PubChem Substance
347910220
ChemSpider
14126465
BindingDB
50122054
ChEBI
64050
ChEMBL
CHEMBL845
ZINC
ZINC000003995781
Wikipedia
Desmethylclozapine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentSchizophrenia1
1CompletedNot AvailableSchizophrenia1

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
PropertyValueSource
Water Solubility0.203 mg/mLALOGPS
logP3.25ALOGPS
logP3.02ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.9ChemAxon
pKa (Strongest Basic)8.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area39.66 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity92.06 m3·mol-1ChemAxon
Polarizability33.57 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Targets

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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