Pimavanserin

Clinical data
Trade names	Nuplazid
Other names	ACP-103; BVF-036; BVF-048
License data	US DailyMed: Pimavanserin
Routes of administration	Oral[1]
Drug class	Serotonin 5-HT2A receptor antagonist;Antipsychotic
ATC code	N05AX17 (WHO)
Legal status
Legal status	US: ℞-only[1]
Pharmacokinetic data
Protein binding	94–97%[2]
Metabolism	Hepatic (CYP3A4,CYP3A5,CYP2J2)[1]
Metabolites	N-Desmethyl-pimavanserin
Onset of action	TmaxTooltip Time to peak levels: 6 hours[3][4][5]
Eliminationhalf-life	Pimavanserin: 54–57 h[2][6] N-Desmethyl-pimavanserin (active): 200 h[6]
Identifiers
IUPAC name N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl)carbamide
CAS Number	706779-91-1 Y 706782-28-7 (tartrate)
PubChemCID	10071196
DrugBank	DB05316 Y
ChemSpider	8246736 Y
UNII	JZ963P0DIK
KEGG	D08969 Y
ChEBI	CHEBI:133017 Y
ChEMBL	ChEMBL2111101 Y
CompTox Dashboard(EPA)	DTXSID90990906
Chemical and physical data
Formula	C25H34FN3O2
Molar mass	427.564 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)COc3ccc(cc3)CNC(=O)N(C(CC2)CCN2C)Cc(cc1)ccc1F
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) N Key:RKEWSXXUOLRFBX-UHFFFAOYSA-N N
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Pimavanserin, sold under the brand nameNuplazid, is anatypical antipsychotic which is approved for the treatment ofParkinson's diseasepsychosis.^[6][7] It is takenby mouth.^[6]

Side effects of pimavanserin includeperipheral edema andconfusion.^[6] Unlike otherantipsychotics, pimavanserin is not adopamine receptor antagonist,^[8] but rather is aselectiveantagonist orinverse agonist of theserotonin5-HT_2A receptor and to a lesser extent of the serotonin5-HT_2C receptor.^[6]

Pimavanserin was first approved for medical use in 2016.^[6] It was approved as ageneric medication in 2024.^[9]

Pimavanserin is used in the treatment ofParkinson's diseasepsychosis.^[6]

Pimavanserin is available in the form of 10 mgoraltablets and 34 mg oralcapsules.^[6]

Side effects of pimavanserin includeperipheral edema andconfusion, among others.^[6]

Pimavanserin acts as aselectiveinverse agonist orantagonist of theserotonin5-HT_2A receptor.^{[2][13][12][14]} It is also an antagonist or inverse agonist of theserotonin5-HT_2C receptor to a lesser extent.^[6]

The drug has anaffinity (K_i) of 0.087 to 0.5 nM for the serotonin 5-HT_2A receptor and 0.44 to 10 nM at the serotonin 5-HT_2C receptor, whereas its functional inhibition (IC₅₀Tooltip half-maximal inhibitory concentration) values have been reported to be 1.9 nM at the serotonin 5-HT_2A receptor and 91 nM at the serotonin 5-HT_2C receptor.^[12][13] Hence, it shows 3- to 50-fold greater affinity for the serotonin 5-HT_2A receptor over the serotonin 5-HT_2C receptor depending on theassay and 49-fold selectivity in terms of functional inhibition of the serotonin 5-HT_2A receptor compared to the serotonin 5-HT_2C receptor.^[12]

Pimavanserin shows low binding toσ₁ receptors (K_i = 120 nM) and has no appreciable affinity (K_i > 300 nM) to serotonin5-HT_2B,dopamine (includingD₂),muscarinic acetylcholine,histamine, oradrenergic receptors, or tocalcium channels.^[1][15]

Pimavanserin is slowslyabsorbed and has atime to peak levels of 6 hours.^[3][4][5] Theelimination half-life of pimavanserin is 54 to 57 hours.^[2][6] The half-life of itsactive metaboliteN-desmethylpimavanserin is 200 hours.^[6]

Pimavanserin was developed byAcadia Pharmaceuticals.

Pimavanserin is expected to improve theeffectiveness andside effect profile of antipsychotics.^[16][17][18] The results of a clinical trial examining the efficacy, tolerability and safety of adjunctive pimavanserin torisperidone andhaloperidol were published in November 2012, and the results showed that pimavanserin potentiated the antipsychotic effects of subtherapeutic doses ofrisperidone and improved the tolerability ofhaloperidol treatment by reducing the incidence ofextrapyramidal symptoms.^[19]

The drug met expectations for aPhase IIIclinical trial for the treatment ofParkinson's diseasepsychosis,^[20] and has completedPhase II trials foradjunctive treatment ofschizophrenia alongside anantipsychotic medication.^[21]

In September 2014, the United StatesFood and Drug Administration (FDA) grantedbreakthrough therapy status to Acadia'sNew Drug Application for pimavanserin.^[22]

In April 2016, Nuplazid (pimavanserin) was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.^[23][24] The non-binding advisory panel recommendation of 12-to-2 in support of approval that preceded the FDA approval action noted that the drug met an important need, despite its only providing modest benefits and posing serious safety issues.^[25]

In June 2018, the FDA approved new dosages of pimavanserin to treat hallucinations and delusions associated with Parkinson's disease psychosis. A 34 mg capsule and 10 mg tablet formulation were approved. Previously, people were required to take two 17 mg tablets to achieve the recommended 34 mg dose per day. The 10 mg dose is indicated for people also takingCYP3A4 inhibitors (e.g.,ketoconazole).^[26]

In a Phase III, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov number NTC03325556) pimavanserin was given to people with dementia-related psychosis. The dementia was caused byAlzheimer's disease,dementia with lewy bodies,frontotemporal dementia, Parkinson's disease dementia, orvascular dementia. The trial was stopped early due to lack of efficacy. People treated with pimavanserin had a relapse in 13%, and those without 28%. Longer and larger trials are suggested.^[27]

In April 2018,CNN reported that some in the FDA were concerned that pimavanserin (Nuplazid) was "risky" when it was approved and noted there have been a substantial number of deaths reported by those using the drug. The story further noted that the drug was approved based on a "six-week study of about 200 patients".^[28] The FDA began post-market monitoring of the drug to assess the validity of these claims.^[29] In September 2018, the FDA stated their review "did not identify any new or unexpected safety findings with Nuplazid, or findings that are inconsistent with the established safety profile currently described in the drug label".^[30]

Pimavanserin was studied as a therapeutic agent in Phase III clinical trials for major depressive disorder and schizophrenia and Phase II trials for agitation. It was also under development for the treatment ofinsomnia, drug-inducedakathisia, and drug-induceddyskinesia, but development for these indications was discontinued.^[7]

In March 2024, Acadia Pharmaceuticals announced its decision to stop any further clinical trials of pimavanserin after the drug did not improve negative symptoms of schizophrenia better than placebo.^[31]

As of November 2024, aphase 2clinical trial is underway assessing the ability of pimavanserin toblock the effects of theserotonergic psychedelicpsilocybin.^[32]

• Serotonin 5-HT_2A receptor antagonist

• 5-HT2A antagonists
• 5-HT2C antagonists
• Atypical antipsychotics
• Experimental antidepressants
• Experimental drugs developed for schizophrenia
• Experimental psychiatric drugs
• 4-Fluorophenyl compounds
• Hallucinogen antidotes
• Inverse agonists
• Phenol ethers
• Piperidines
• Ureas

• Articles with short description
• Short description is different from Wikidata
• Use dmy dates from October 2025
• Articles with changed InChI identifier