Pimavanserin

Summary

Pimavanserin (CHEMBL2111101) is an approved small-molecule antipsychotic agent (ATC N05AX17) targeting HTR2A; indicated across 6 conditions including psychotic disorder and neurodegenerative disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AX17
• Targets: 1 (HTR2A)
• Indications: 6 conditions
• Clinical trials: 31
• Chemistry: 427.6 Da · C25H34FN3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2111101
Name	Pimavanserin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	10071196
ChEBI	CHEBI:133017
ATC	N05AX17
Molecular formula	C25H34FN3O2
Molecular weight	427.6
InChIKey	RKEWSXXUOLRFBX-UHFFFAOYSA-N

SMILES: CC(C)COC1=CC=C(C=C1)CNC(=O)N(CC2=CC=C(C=C2)F)C3CCN(CC3)C

IUPAC name: 1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-[[4-(2-methylpropoxy)phenyl]methyl]urea

ChEBI definition: A member of the class of ureas in which three of the four hydrogens are replaced by 4-fluorobenzyl, 1-methylpiperidin-4-yl, and 4-(isopropyloxy)benzyl groups. An atypical antipsychotic that is used (in the form of its tartrate salt) for treatment of hallucinations and delusions associated with Parkinson’s disease.

Pharmacological roles (ChEBI): antipsychotic agent, 5-hydroxytryptamine 2A receptor inverse agonist, serotonergic antagonist.

Also known as: Pimavanserin, Pimavanserina, Pimavanserine, PIMAVANSERIN, pimavanserin, Pimavanserin; Nuplazid

Parent form; salt/anhydrous children: CHEMBL2448613, CHEMBL5177911

Patent coverage: 535 distinct patent families (1,357 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
HTR2A	5-HT2A receptor	Inverse agonist	9.3	0%	P28223

Broader ChEMBL bioactivity targets: 23 (assay-derived). Sample: G-protein coupled receptor 35, Apelin receptor, D(1A) dopamine receptor, Thromboxane A2 receptor, Beta-2 adrenergic receptor, Muscarinic acetylcholine receptor M2, Muscarinic acetylcholine receptor M1, Sodium-dependent noradrenaline transporter, 5-hydroxytryptamine receptor 2A, 5-hydroxytryptamine receptor 2C.

Bioactivity

ChEMBL activities: 32 potent at pChembl ≥ 5 of 41 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	10.2	Ki	0.06	nM	CHEMBL_ACT_25511285
HTR2A	9.7	Ki	0.2	nM	CHEMBL_ACT_26005147
HTR2A	9.3	Ki	0.5	nM	CHEMBL_ACT_24710289
HTR2A	9.3	Ki	0.5	nM	CHEMBL_ACT_25511271
HTR2A	9.07	Ki	0.86	nM	CHEMBL_ACT_26005177
HTR2C	8.82	Ki	1.5	nM	CHEMBL_ACT_24710290
HTR2A	8.73	IC50	1.86	nM	CHEMBL_ACT_25001813
HTR2A	8.3	IC50	5.01	nM	CHEMBL_ACT_25511297
HTR2C	8.24	Ki	5.72	nM	CHEMBL_ACT_26005185
HTR2A	8.05	IC50	9	nM	CHEMBL_ACT_18530238
HTR2C	8	Ki	10	nM	CHEMBL_ACT_26005148
HTR2A	7.99	IC50	10.36	nM	CHEMBL_ACT_29145089
HTR2A	7.9	IC50	12.59	nM	CHEMBL_ACT_25511277
HTR2A	7.9	IC50	12.6	nM	CHEMBL_ACT_25511305
HTR2A	7.66	IC50	22	nM	CHEMBL_ACT_20648304
HTR2A	7.56	IC50	27.3	nM	CHEMBL_ACT_24804012
HTR2A	7.3	IC50	50	nM	CHEMBL_ACT_24804084
HTR2A	7.1	IC50	79.43	nM	CHEMBL_ACT_25511289
KCNH2	6.48	IC50	330	nM	CHEMBL_ACT_26005149
KCNH2	6.39	IC50	410	nM	CHEMBL_ACT_24804065
KCNH2	6.14	AC50	730	nM	CHEMBL_ACT_25118033
DRD3	5.58	AC50	2658	nM	CHEMBL_ACT_25194736
Q01827	5.51	AC50	3100	nM	CHEMBL_ACT_25197377
CX3CR1	5.49	IC50	3258	nM	CHEMBL_ACT_25751419
APLNR	5.46	IC50	3437	nM	CHEMBL_ACT_25751418
GPR65	5.45	IC50	3540	nM	CHEMBL_ACT_25751422
GPR183	5.36	IC50	4330	nM	CHEMBL_ACT_25751420
CHRM2	5.34	AC50	4600	nM	CHEMBL_ACT_25195956
ADRB2	5.34	IC50	4550	nM	CHEMBL_ACT_25751417
GPR35	5.25	IC50	5642	nM	CHEMBL_ACT_25751421

Target pathways

Aggregated over 1 target gene(s): HTR2A.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	HTR2A
Signaling by GPCR	1	HTR2A
Class A/1 (Rhodopsin-like receptors)	1	HTR2A
Amine ligand-binding receptors	1	HTR2A
GPCR downstream signalling	1	HTR2A
Serotonin receptors	1	HTR2A
G alpha (q) signalling events	1	HTR2A
GPCR ligand binding	1	HTR2A

Dominant GO biological processes

GO term	Targets
temperature homeostasis	1
positive regulation of cytokine production involved in immune response	1
glycolytic process	1
intracellular calcium ion homeostasis	1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
positive regulation of cytosolic calcium ion concentration	1
phospholipase C-activating serotonin receptor signaling pathway	1
serotonin receptor signaling pathway	1
chemical synaptic transmission	1
memory	1
positive regulation of cell population proliferation	1
response to xenobiotic stimulus	1
positive regulation of phosphatidylinositol biosynthetic process	1
regulation of dopamine secretion	1
artery smooth muscle contraction	1

Indications & clinical

Indications

6 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
psychotic disorder	4	MONDO:0005485	EFO:0005407
neurodegenerative disease	3	MONDO:0005559	EFO:0005772
major depressive disorder	3	MONDO:0002009	MONDO:0002009
Parkinson disease	2	MONDO:0005180	MONDO:0005180
Tourette syndrome	0	MONDO:0007661	EFO:0004895

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 31.

Phase distribution

Phase	Trials
PHASE2	10
PHASE3	8
PHASE4	6
PHASE2/PHASE3	2
EARLY_PHASE1	2
PHASE1/PHASE2	1
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04373317	PHASE4	RECRUITING	Pimavanserin vs. Quetiapine for Treatment of Parkinson’s Psychosis
NCT05357612	PHASE4	RECRUITING	Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases
NCT05590637	PHASE4	RECRUITING	Comparing Antipsychotic Medications in LBD Over Time
NCT04188392	PHASE4	COMPLETED	Pimavanserin for Insomnia In Veterans With Posttraumatic Stress Disorder
NCT04292223	PHASE4	COMPLETED	Open-Label Study With Pimavanserin on Activities of Daily Living in Subjects With Parkinson’s Disease Psychosis
NCT04809116	PHASE4	WITHDRAWN	Pimavanserin for Insomnia in Veterans With Posttraumatic Stress Disorder: Proof of Concept
NCT02970292	PHASE3	COMPLETED	Efficacy and Safety of Adjunctive Pimavanserin for the Treatment of Schizophrenia (ENHANCE-1)
NCT03121586	PHASE3	TERMINATED	Extension Study of Pimavanserin for the Adjunctive Treatment of Schizophrenia
NCT03325556	PHASE3	COMPLETED	Relapse Prevention Study of Pimavanserin in Dementia-related Psychosis
NCT03575052	PHASE3	COMPLETED	A Safety Study of Pimavanserin in Adult and Elderly Subjects Experiencing Neuropsychiatric Symptoms Related to Neurodegenerative Disease
NCT03623321	PHASE3	COMPLETED	Extension Study of Pimavanserin in Adult Subjects With Neuropsychiatric Symptoms Related to Neurodegenerative Disease
NCT03968159	PHASE3	COMPLETED	Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment
NCT04000009	PHASE3	TERMINATED	Extension Study of Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment
NCT04531982	PHASE3	COMPLETED	Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia
NCT05523895	PHASE2/PHASE3	COMPLETED	Pimavanserin for the Treatment of Irritability Associated With Autism Spectrum Disorder
NCT05555615	PHASE2/PHASE3	TERMINATED	Extension Study of Pimavanserin in Irritability Associated With Autism Spectrum Disorder
NCT05441280	PHASE2	RECRUITING	Pimavanserin for Insomnia in Veterans With PTSD
NCT05895513	PHASE2	RECRUITING	Pimavanserin and Aggression and Social Cognition.
NCT06592833	PHASE2	RECRUITING	Psilocybin With Pimavanserin Compared to Psilocybin Alone for the Treatment of Major Depressive Disorder
NCT07610135	PHASE1/PHASE2	NOT_YET_RECRUITING	Psilocybin Efficacy With or Without Pimavanserin Pretreatment
NCT02970305	PHASE2	COMPLETED	Efficacy and Safety of Pimavanserin as Adjunctive Treatment for the Negative Symptoms of Schizophrenia (ADVANCE)
NCT02992132	PHASE2	TERMINATED	Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Agitation and Aggression in Alzheimer’s Disease (SERENE)
NCT03018340	PHASE2	COMPLETED	Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Major Depressive Disorder (CLARITY)
NCT03118947	PHASE2	COMPLETED	A Study of Pimavanserin for the Treatment of Agitation and Aggression in Subjects With Alzheimer’s Disease
NCT03482882	PHASE2	COMPLETED	Safety and Efficacy of Pimavanserin in Adults With Parkinson’s Disease and Depression
NCT03994965	PHASE2	WITHDRAWN	The Sub-Sero Study
NCT04164758	PHASE2	TERMINATED	Study to Evaluate Safety and Daytime Sedation in Subjects With Parkinson’s Disease With Neuropsychiatric Symptoms Treated With Pimavanserin or Low-Dose Quetiapine
NCT06450184	PHASE1	COMPLETED	Bioequivalence Study of Pimavanserin 34 mg Capsule
NCT04794413	EARLY_PHASE1	COMPLETED	Pimavanserin Treatment in TS
NCT05796167	EARLY_PHASE1	WITHDRAWN	Pimavanserin for Sleep in Parkinson Disease
NCT07022366	Not specified	RECRUITING	Investigating the Neuropsychological Effects of 5-HT2a Antagonism

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

387 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A
FIDAXOMICIN	ChEMBL + PubChem	Phase 4 (approved)	HTR2A
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A
ABEMACICLIB	ChEMBL	Phase 4 (approved)	HTR2A
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	HTR2A
ACYCLOVIR	ChEMBL	Phase 4 (approved)	HTR2A
ALMOTRIPTAN	ChEMBL	Phase 4 (approved)	HTR2A
ALOSETRON	ChEMBL	Phase 4 (approved)	HTR2A
AMIODARONE	ChEMBL	Phase 4 (approved)	HTR2A
AMISULPRIDE	ChEMBL	Phase 4 (approved)	HTR2A
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR2A
AMLODIPINE	ChEMBL	Phase 4 (approved)	HTR2A
AMOXAPINE	ChEMBL	Phase 4 (approved)	HTR2A
APOMORPHINE	ChEMBL	Phase 4 (approved)	HTR2A
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A
ASENAPINE	ChEMBL	Phase 4 (approved)	HTR2A
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR2A
ATOMOXETINE	ChEMBL	Phase 4 (approved)	HTR2A
AZATADINE	ChEMBL	Phase 4 (approved)	HTR2A
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR2A
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	HTR2A
BEDAQUILINE	ChEMBL	Phase 4 (approved)	HTR2A
BENFLUOREX	ChEMBL	Phase 4 (approved)	HTR2A
BENPERIDOL	ChEMBL	Phase 4 (approved)	HTR2A
BENZBROMARONE	ChEMBL	Phase 4 (approved)	HTR2A
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	HTR2A
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	HTR2A
BENZTROPINE	ChEMBL	Phase 4 (approved)	HTR2A
BEPRIDIL	ChEMBL	Phase 4 (approved)	HTR2A
BIFONAZOLE	ChEMBL	Phase 4 (approved)	HTR2A
BLONANSERIN	ChEMBL	Phase 4 (approved)	HTR2A
BOSUTINIB	ChEMBL	Phase 4 (approved)	HTR2A
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	HTR2A
BROMPERIDOL	ChEMBL	Phase 4 (approved)	HTR2A
BUSPIRONE	ChEMBL	Phase 4 (approved)	HTR2A
BUTENAFINE	ChEMBL	Phase 4 (approved)	HTR2A
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR2A
CABERGOLINE	ChEMBL	Phase 4 (approved)	HTR2A
CABOZANTINIB	ChEMBL	Phase 4 (approved)	HTR2A
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	HTR2A
CANNABIDIOL	ChEMBL	Phase 4 (approved)	HTR2A
CAPTOPRIL	ChEMBL	Phase 4 (approved)	HTR2A
CARBENOXOLONE	ChEMBL	Phase 4 (approved)	HTR2A
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR2A
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR2A
CETIRIZINE	ChEMBL	Phase 4 (approved)	HTR2A
CHLOPHEDIANOL	ChEMBL	Phase 4 (approved)	HTR2A
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	HTR2A
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	HTR2A
CHLORPHENTERMINE	ChEMBL	Phase 4 (approved)	HTR2A
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	HTR2A
CHLORPROPAMIDE	ChEMBL	Phase 4 (approved)	HTR2A
CINACALCET	ChEMBL	Phase 4 (approved)	HTR2A
CINNARIZINE	ChEMBL	Phase 4 (approved)	HTR2A
CISAPRIDE	ChEMBL	Phase 4 (approved)	HTR2A
CITALOPRAM	ChEMBL	Phase 4 (approved)	HTR2A
CLEMASTINE	ChEMBL	Phase 4 (approved)	HTR2A
CLINDAMYCIN	ChEMBL	Phase 4 (approved)	HTR2A
CLOFIBRATE	ChEMBL	Phase 4 (approved)	HTR2A