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Identification
NamePimavanserin
Accession NumberDB05316
TypeSmall Molecule
GroupsInvestigational
Description

Pimavanserin (ACP-103), marketed under the trade name Nuplazid, is a drug developed by Acadia Pharmaceuticals which acts as an inverse agonist on the serotonin receptor subtype 5-HT2A, with 40x selectivity over 5-HT2C, and no significant affinity or activity at 5-HT2B or dopamine receptors. As of September 3, 2009, pimavanserin has not met expectations for Phase III clinical trials for the treatment of Parkinson’s disease psychosis, and is in Phase II trials for adjunctive treatment of schizophrenia alongside an antipsychotic medication. It is expected to improve the effectiveness and side effect profile of antipsychotics. The results of a clinical trial examining the efficacy, tolerability and safety of adjunctive pimavanserin to risperidone and haloperidol were published in November 2012 and the results showed that pimavanserin potentiated the antipsychotic effects of subtherapeutic doses of risperidone and improve the tolerability of haloperidol treatment by reducing the incidence of extrapyramidal symptoms. On September 2, 2014, the United States Food and Drug administration granted Breakthrough Therapy status to Acadia’s New Drug Application for pimavanserin.

Structure
Thumb
SynonymsNot Available
External Identifiers
  • ACP 103
  • ACP-103
  • ACP103
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Pimavanserin tartrate
706782-28-7
Thumb
  • InChI Key: RGSULKHNAKTFIZ-CEAXSRTFSA-N
  • Monoisotopic Mass: 1004.543449028
  • Average Mass: 1005.1964
DBSALT001266
Categories
UNIIJZ963P0DIK
CAS number706779-91-1
WeightAverage: 427.564
Monoisotopic: 427.26350551
Chemical FormulaC25H34FN3O2
InChI KeyRKEWSXXUOLRFBX-UHFFFAOYSA-N
InChI
InChI=1S/C25H34FN3O2/c1-19(2)18-31-24-10-6-20(7-11-24)16-27-25(30)29(23-12-14-28(3)15-13-23)17-21-4-8-22(26)9-5-21/h4-11,19,23H,12-18H2,1-3H3,(H,27,30)
IUPAC Name
1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-{[4-(2-methylpropoxy)phenyl]methyl}urea
SMILES
CC(C)COC1=CC=C(CNC(=O)N(CC2=CC=C(F)C=C2)C2CCN(C)CC2)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenol ethers
Sub ClassNot Available
Direct ParentPhenol ethers
Alternative Parents
Substituents
  • Phenoxy compound
  • Benzylamine
  • Phenol ether
  • Alkyl aryl ether
  • Fluorobenzene
  • Halobenzene
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Piperidine
  • Urea
  • Tertiary aliphatic amine
  • Tertiary amine
  • Organoheterocyclic compound
  • Ether
  • Azacycle
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Organooxygen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in neurologic disorders, parkinson's disease, psychosis, schizophrenia and schizoaffective disorders, and sleep disorders.
PharmacodynamicsNot Available
Mechanism of actionACP-103 reduces haloperidol-induced akathisia, a debilitating extrapyramidal side effect (EPS), in patients with schizophrenia. ACP-103 is a 5-HT2A inverse agonist, to reduce the side effects associated with antipsychotic drug treatment with haloperidol. ACP-103 reduced both the motor disturbances and hyperprolactinemia, a condition of elevated prolactin secretion, caused by haloperidol treatment.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.696
Blood Brain Barrier-0.8018
Caco-2 permeable-0.6395
P-glycoprotein substrateSubstrate0.8782
P-glycoprotein inhibitor INon-inhibitor0.685
P-glycoprotein inhibitor IINon-inhibitor0.8743
Renal organic cation transporterNon-inhibitor0.799
CYP450 2C9 substrateNon-substrate0.7844
CYP450 2D6 substrateNon-substrate0.8342
CYP450 3A4 substrateSubstrate0.5769
CYP450 1A2 substrateNon-inhibitor0.8285
CYP450 2C9 inhibitorNon-inhibitor0.7474
CYP450 2D6 inhibitorNon-inhibitor0.8458
CYP450 2C19 inhibitorNon-inhibitor0.8247
CYP450 3A4 inhibitorNon-inhibitor0.9552
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8855
Ames testNon AMES toxic0.6638
CarcinogenicityNon-carcinogens0.8967
BiodegradationNot ready biodegradable0.9775
Rat acute toxicity2.4414 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8668
hERG inhibition (predictor II)Inhibitor0.7703
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00748 mg/mLALOGPS
logP4.19ALOGPS
logP4.01ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)15.06ChemAxon
pKa (Strongest Basic)8.44ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area44.81 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity122.93 m3·mol-1ChemAxon
Polarizability47.76 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Nordstrom AL, Mansson M, Jovanovic H, Karlsson P, Halldin C, Farde L, Vanover KE, Hacksell U, Brann MR, Davis RE, Weiner DM: PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain. Int J Neuropsychopharmacol. 2008 Mar;11(2):163-71. Epub 2007 Aug 21. [PubMed:17708779 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inverse agonist
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
References
  1. Friedman JH: Pimavanserin for the treatment of Parkinson's disease psychosis. Expert Opin Pharmacother. 2013 Oct;14(14):1969-75. doi: 10.1517/14656566.2013.819345. [PubMed:24016069 ]
Kind
Protein
Organism
Human
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
Molecular Weight:
50618.91 Da
Comments
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Drug created on November 18, 2007 11:23 / Updated on January 18, 2016 12:58