Prochlorperazine

Summary

Prochlorperazine (CHEMBL728) is an approved small-molecule dopaminergic antagonist (ATC N05AB04) targeting DRD1, DRD2, and DRD3; indicated across 11 conditions including psychotic disorder and anxiety disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AB04
• Targets: 4 (DRD1, DRD2, DRD3…)
• Indications: 11 conditions
• Clinical trials: 24
• Chemistry: 373.9 Da · C20H24ClN3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL728
Name	Prochlorperazine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4917
ChEBI	CHEBI:8435
ATC	N05AB04
Molecular formula	C20H24ClN3S
Molecular weight	373.9
InChIKey	WIKYUJGCLQQFNW-UHFFFAOYSA-N

SMILES: CN1CCN(CC1)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)Cl

IUPAC name: 2-chloro-10-[3-(4-methylpiperazin-1-yl)propyl]phenothiazine

ChEBI definition: A member of the class of phenothiazines that is 10H-phenothiazine having a chloro substituent at the 2-position and a 3-(4-methylpiperazin-1-yl)propyl group at the N-10 position.

Pharmacological roles (ChEBI): antiemetic, dopaminergic antagonist, α-adrenergic antagonist, cholinergic antagonist, first generation antipsychotic, EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, dopamine receptor D2 antagonist.

Also known as: Compazine, Compro, Prochlorperazine, Prochlorperazine mesilate, Prochlorperazine mesylate, Proclorperazina, Stemetil eff, prochlorperazine, SID11111685, SID11111686, SID855827, SID90341442

Parent form; salt/anhydrous children: CHEMBL1201154, CHEMBL1314751

Patent coverage: 6,489 distinct patent families (25,844 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 25,690 (99%) of the total. 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
DRD1	D1 receptor	Antagonist	7.11	0%	P21728
DRD2	D2 receptor	Antagonist	8.44	0%	P14416
DRD3	D3 receptor	Antagonist	8.35	0%	P35462
DRD4	D4 receptor	Antagonist	6.09	0%	P21917

Broader ChEMBL bioactivity targets: 66 (assay-derived). Sample: Microtubule-associated protein tau, Nuclear receptor ROR-gamma, Survival motor neuron protein, Fructose-bisphosphate aldolase, Prelamin-A/C, 4’-phosphopantetheinyl transferase ffp, Thrombopoietin, Pleiotropic ABC efflux transporter of multiple drugs, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B.

Bioactivity

ChEMBL activities: 99 potent at pChembl ≥ 5 of 138 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	8.7	Ki	2.02	nM	CHEMBL_ACT_7745776
HRH1	8.55	Ki	2.79	nM	CHEMBL_ACT_7743638
DRD2	8.44	Ki	3.61	nM	CHEMBL_ACT_7743606
DRD3	8.35	Ki	4.45	nM	CHEMBL_ACT_7743608
ADRA2B	8.32	Ki	4.74	nM	CHEMBL_ACT_7743538
HTR2A	8.15	IC50	7.06	nM	CHEMBL_ACT_7745775
ADRA2B	8	IC50	10	nM	CHEMBL_ACT_7743537
DRD2	7.96	IC50	11	nM	CHEMBL_ACT_7743605
ADRA2C	7.92	Ki	12	nM	CHEMBL_ACT_7743540
P43140	7.89	Ki	13	nM	CHEMBL_ACT_7743530
DRD3	7.89	IC50	13	nM	CHEMBL_ACT_7743607
ADRA1D	7.8	Ki	16	nM	CHEMBL_ACT_7743534
SIGMAR1	7.64	Ki	23	nM	CHEMBL_ACT_7745790
HRH1	7.62	IC50	24	nM	CHEMBL_ACT_7743637
HTR2A	7.59	AC50	25.4	nM	CHEMBL_ACT_25173764
P43140	7.5	IC50	32	nM	CHEMBL_ACT_7743529
ADRA1D	7.47	IC50	34	nM	CHEMBL_ACT_7743533
HTR2C	7.39	Ki	41	nM	CHEMBL_ACT_7745780
DRD2	7.36	AC50	44	nM	CHEMBL_ACT_25140801
P15823	7.31	Ki	49	nM	CHEMBL_ACT_7743532
DRD3	7.28	AC50	52	nM	CHEMBL_ACT_25193984
SIGMAR1	7.27	IC50	54	nM	CHEMBL_ACT_7745789
ADRA2A	7.2	Ki	63	nM	CHEMBL_ACT_7743536
HTR2B	7.19	Ki	65	nM	CHEMBL_ACT_7745778
DRD1	7.11	Ki	78	nM	CHEMBL_ACT_7743604
HTR2C	7.11	IC50	78	nM	CHEMBL_ACT_7745779
ADRA2C	7.09	IC50	82	nM	CHEMBL_ACT_7743539
LMNA	7.05	Potency	89.1	nM	CHEMBL_ACT_3644879
P15823	7.05	IC50	89	nM	CHEMBL_ACT_7743531
HTR2B	6.99	IC50	102	nM	CHEMBL_ACT_7745777

Target pathways

Aggregated over 4 target gene(s): DRD1, DRD2, DRD3, DRD4.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Dopamine receptors	4	DRD1, DRD2, DRD3, DRD4
G alpha (i) signalling events	2	DRD3, DRD4
G alpha (s) signalling events	1	DRD1

Dominant GO biological processes

GO term	Targets
behavioral response to cocaine	4
phospholipase C-activating dopamine receptor signaling pathway	4
synaptic transmission, dopaminergic	4
signal transduction	4
G protein-coupled receptor signaling pathway	4
response to amphetamine	3
visual learning	3
response to xenobiotic stimulus	3
dopamine metabolic process	3
regulation of dopamine uptake involved in synaptic transmission	3
locomotory behavior	3
response to cocaine	3
prepulse inhibition	3
intracellular calcium ion homeostasis	3
adenylate cyclase-inhibiting dopamine receptor signaling pathway	3

Indications & clinical

Indications

11 indications (4 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
anxiety disorder	4	MONDO:0005618	EFO:0006788
migraine disorder	3	MONDO:0005277	MONDO:0005277
female reproductive organ cancer	3	MONDO:0001416	EFO:1001331
plasma cell myeloma	0	MONDO:0009693	EFO:0001378

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

Clinical trials

Total trials: 24.

Phase distribution

Phase	Trials
PHASE3	7
PHASE4	6
PHASE2	5
Not specified	3
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00364806	PHASE4	COMPLETED	Prochlorperazine vs Metoclopramide
NCT01629329	PHASE4	TERMINATED	Prochlorperazine Versus Acetaminophen, Aspirin, and Caffeine for the Treatment of Acute Migraine
NCT02389829	PHASE4	COMPLETED	Hydromorphone Versus Prochlorperazine + Diphenhydramine for Acute Migraine
NCT02657031	PHASE4	COMPLETED	The CHECK Trial: A Comparison of Headache Treatment in the ED: Compazine Versus Ketamine
NCT03435003	PHASE4	COMPLETED	Designing Optimal Prevention and Management of Postoperative Nausea and Emesis for Patients Undergoing Laparoscopic Sleeve Gastrectomy
NCT06310642	PHASE4	COMPLETED	Efficacy of Prophylactic Treatment of Oral Prochlorperazine for Acute Mountain Sickness
NCT00020657	PHASE3	COMPLETED	Comparison of Antiemetic Drugs in Preventing Delayed Nausea After Chemotherapy in Patients With Cancer
NCT00475085	PHASE3	COMPLETED	Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial
NCT02735343	PHASE3	TERMINATED	The CHECK Trial: A Comparison of Headache Treatment in the Emergency Department: Compazine Versus Ketamine
NCT02779959	PHASE3	UNKNOWN	Buccal Prochlorperazine Versus Intravenous Prochlorperazine for Migraine Headaches, a RCT
NCT03367572	PHASE3	COMPLETED	Treatment of Refractory Nausea and Vomiting in Patients With Breast Cancer
NCT03984045	PHASE3	UNKNOWN	SPG Block for Acute Pediatric Migraine
NCT04503668	PHASE3	TERMINATED	Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Gynecologic Oncology Patients
NCT00001337	PHASE2	COMPLETED	Dose-Adjusted EPOCH Chemotherapy and Rituximab (CD20+) in Previously Untreated Aggressive Non-Hodgkin’s Lymphoma
NCT00590317	PHASE2	COMPLETED	Ondansetron vs Prochlorperazine for Nausea and Vomiting in the Emergency Department
NCT01391962	PHASE2	COMPLETED	Sunitinib or Cediranib for Alveolar Soft Part Sarcoma
NCT01851369	PHASE1/PHASE2	COMPLETED	TRC102 and Temozolomide for Relapsed Solid Tumors and Lymphomas
NCT02858310	PHASE1/PHASE2	COMPLETED	E7 TCR T Cells for Human Papillomavirus-Associated Cancers
NCT04109885	PHASE2	TERMINATED	Paracervical Injection for Headache in the Emergency Department
NCT06083571	PHASE2	TERMINATED	Intranasal Ketorolac Trial
NCT05013437	EARLY_PHASE1	WITHDRAWN	Melphalan on Disease Burden Measured by Next Generation Sequencing Before AHCT (Autologous Hematopoietic Cell Transplant) for Multiple Myeloma
NCT00573599	Not specified	WITHDRAWN	Prochlorperazine vs Imitrex for Acute Migraine in the Emergency Department
NCT02600741	Not specified	COMPLETED	Family Intervention in Recent Onset Schizophrenia Treatment (FIRST)
NCT06182098	Not specified	UNKNOWN	Intravenous Fluids in Pediatric Migraine

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 2 clinical and 7 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
DISULFIRAM	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
DOBUTAMINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
DOPAMINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
EBASTINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ECONAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ILOPERIDONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
IMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
LOPERAMIDE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
LOXAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
MECLIZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
MICONAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
OLANZAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
PERGOLIDE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
PIMOZIDE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
PROMETHAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
QUETIAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
RISPERIDONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ROPINIROLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ROTIGOTINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
SERTINDOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
SILODOSIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
SULPIRIDE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
SUNITINIB	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
TAMOXIFEN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
TEGASEROD	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
THIOTHIXENE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
TRAZODONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD3, DRD4
LISURIDE	ChEMBL	Phase 3	DRD1, DRD2, DRD3, DRD4
LEVOSULPIRIDE	ChEMBL	Phase 2	DRD1, DRD2, DRD3, DRD4
PENFLURIDOL	ChEMBL	Phase 2	DRD1, DRD2, DRD3, DRD4
QUINPIROLE	ChEMBL	Phase 2	DRD1, DRD2, DRD3, DRD4