Pimavanserin

Identification

Name
Pimavanserin
Accession Number
DB05316
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. It is in Phase II trials for adjunctive treatment of schizophrenia alongside an antipsychotic medication and 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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 427.564
Monoisotopic: 427.26350551
Chemical Formula
C25H34FN3O2
Synonyms
  • Pimavanserin
External IDs
  • ACP 103
  • ACP-103
  • ACP103

Pharmacology

Indication

Investigated for use/treatment in neurologic disorders, parkinson's disease, psychosis, schizophrenia and schizoaffective disorders, and sleep disorders.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics
Not Available
Mechanism of action

ACP-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.

TargetActionsOrganism
A5-hydroxytryptamine receptor 2A
inverse agonist
Humans
UDopamine D2 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
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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.
DrugInteraction
AcenocoumarolThe risk or severity of adverse effects can be increased when Pimavanserin is combined with Acenocoumarol.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Pimavanserin.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Pimavanserin.
AclidiniumPimavanserin may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Pimavanserin is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Pimavanserin.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Pimavanserin.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Pimavanserin.
AlosetronThe risk or severity of adverse effects can be increased when Alosetron is combined with Pimavanserin.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Pimavanserin.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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Food Interactions
  • Avoid grapefruit products. Dose adjustment may be necessary if taking grapefruit products or other CYP3A4 inhibitors.
  • Avoid St. John's Wort. This may induce the CYP3A4 metabolism of pimavanserin, which may cause reduced efficacy.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pimavanserin tartrateNA83F1SJSR706782-28-7RGSULKHNAKTFIZ-CEAXSRTFSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NuplazidTablet, coated10 mg/1OralACADIA Pharmaceuticals Inc2018-06-28Not applicableUS flag
NuplazidTablet, coated17 mg/1OralACADIA Pharmaceuticals Inc2016-04-292022-04-30US flag
NuplazidCapsule34 mg/1OralACADIA Pharmaceuticals Inc2018-06-28Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
N05AX17 — Pimavanserin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Fluorobenzenes / Alkyl aryl ethers / Piperidines / Aryl fluorides / Ureas / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organofluorides
show 3 more
Substituents
Alkyl aryl ether / Amine / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Carbonic acid derivative / Carbonyl group / Ether / Fluorobenzene
show 18 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
JZ963P0DIK
CAS number
706779-91-1
InChI Key
RKEWSXXUOLRFBX-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

References

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]
PubChem Compound
10071196
PubChem Substance
175426976
ChemSpider
8246736
BindingDB
139370
RxNav
1791685
ChEBI
133017
ChEMBL
CHEMBL2111101
ZINC
ZINC000016159083
Wikipedia
Pimavanserin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentInsomnia / Post Traumatic Stress Disorder (PTSD)1
4Not Yet RecruitingTreatmentParkinson's Disease Psychosis1
4RecruitingTreatmentParkinson's Disease Psychosis1
3Active Not RecruitingTreatmentAdjunctive Treatment of Major Depressive Disorder1
3CompletedTreatmentAdjunctive Treatment of Major Depressive Disorder2
3CompletedTreatmentDementia-related Psychosis1
3CompletedTreatmentParkinson's Disease Psychosis4
3CompletedTreatmentSchizophrenia1
3RecruitingTreatmentNeuropsychiatric Symptoms Related to Neurodegenerative Disease2
3RecruitingTreatmentSchizophrenia2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral34 mg/1
Tablet, coatedOral10 mg/1
Tablet, coatedOral17 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9296694No2016-03-292021-03-06US flag
US8110574No2012-02-072020-12-13US flag
US7601740No2009-10-132027-06-17US flag
US7732615No2010-06-082028-06-03US flag
US7923564No2011-04-122025-09-26US flag
US6756393No2004-06-292021-03-06US flag
US7858789No2010-12-282020-12-13US flag
US7115634No2006-10-032021-10-06US flag
US7659285No2010-02-092026-08-24US flag
US6815458No2004-11-092021-03-06US flag
US8618130No2013-12-312024-01-15US flag
US8921393No2014-12-302024-01-15US flag
US9566271No2017-02-142024-01-15US flag
US9765053No2017-09-192022-07-27US flag
US10028944No2018-07-242024-01-15US flag
US10449185No2019-10-222038-08-27US flag
US10517860No2019-12-312037-03-23US flag
US10646480No2018-08-272038-08-27US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not 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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
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-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
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
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

Drug created on November 18, 2007 11:23 / Updated on June 12, 2020 10:52

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