Piribedil

Summary

Piribedil (CHEMBL1371770) is a phase-3 clinical-stage small molecule (ATC N04BC08) targeting HTR1A, DRD2, and DRD3; indicated across 1 condition including parkinson disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: N04BC08
• Targets: 8 (HTR1A, DRD2, DRD3…)
• Indications: 1 condition
• Clinical trials: 5
• Chemistry: 298.34 Da · C16H18N4O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1371770
Name	Piribedil
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	4850
ATC	N04BC08
Molecular formula	C16H18N4O2
Molecular weight	298.34
InChIKey	OQDPVLVUJFGPGQ-UHFFFAOYSA-N

SMILES: C1CN(CCN1CC2=CC3=C(C=C2)OCO3)C4=NC=CC=N4

IUPAC name: 2-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]pyrimidine

Also known as: ET-495, EU-4200, Piribedil, Trivastal, Trivastal lp, SID11111687, SID11111688, SID11113867, SID90341513, SID104171222, PIRIBEDIL, SID144203796

Parent form; salt/anhydrous children: CHEMBL1256997, CHEMBL1468572, CHEMBL1865834, CHEMBL4594075

Patent coverage: 1,296 distinct patent families (4,704 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,651 (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
HTR1A	5-HT1A receptor	Partial agonist	6.4	0%	P08908
DRD2	D2 receptor	Partial agonist	6.9	0%	P14416
DRD3	D3 receptor	Partial agonist	6.6	0%	P35462
DRD4	D4 receptor	Antagonist	6.5	0%	P21917
ADRA1A	α1A-adrenoceptor	Antagonist	6.1		P35348
ADRA2A	α2A-adrenoceptor	Antagonist	7.1	0.1%	P08913
ADRA2C	α2C-adrenoceptor	Antagonist	7.2	0%	P18825
HTR2B	5-HT2B receptor	Antagonist	5.9	0.4%	P41595

Broader ChEMBL bioactivity targets: 21 (assay-derived). Sample: Ubiquitin carboxyl-terminal hydrolase 2, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Menin/Histone-lysine N-methyltransferase MLL, 5-hydroxytryptamine receptor 1A, D(2) dopamine receptor, Sodium-dependent noradrenaline transporter, Sodium-dependent serotonin transporter.

Bioactivity

ChEMBL activities: 31 potent at pChembl ≥ 5 of 39 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADRA2A	7.23	AC50	59	nM	CHEMBL_ACT_25220506
NFKB1	6.95	Potency	112.2	nM	CHEMBL_ACT_3672776
NFKB1	6.95	Potency	112.2	nM	CHEMBL_ACT_4586057
CYP2D6	6.7	Potency	199.5	nM	CHEMBL_ACT_4994169
CYP2D6	6.7	AC50	199.5	nM	CHEMBL_ACT_5988357
MAPK1	6.3	Potency	501.2	nM	CHEMBL_ACT_4549278
CYP2C19	6.2	Potency	631	nM	CHEMBL_ACT_4019395
CYP2C19	6.2	AC50	631	nM	CHEMBL_ACT_6047902
ADRA2C	6.02	AC50	960	nM	CHEMBL_ACT_25148529
CYP2D6	6	Potency	1000	nM	CHEMBL_ACT_4949733
CYP2D6	6	AC50	1000	nM	CHEMBL_ACT_5986800
CYP2C19	5.7	Potency	1995	nM	CHEMBL_ACT_4015582
CYP1A2	5.7	AC50	1995	nM	CHEMBL_ACT_6043041
CYP2C19	5.7	AC50	1995	nM	CHEMBL_ACT_6056331
HTR2B	5.64	AC50	2300	nM	CHEMBL_ACT_25228134
CYP3A4	5.5	Potency	3162	nM	CHEMBL_ACT_4973718
CYP3A4	5.5	Potency	3162	nM	CHEMBL_ACT_4998010
CYP3A4	5.5	Potency	3162	nM	CHEMBL_ACT_5042744
CYP3A4	5.5	Potency	3162	nM	CHEMBL_ACT_5066762
CYP3A4	5.5	AC50	3162	nM	CHEMBL_ACT_6027471
CYP3A4	5.5	AC50	3162	nM	CHEMBL_ACT_6044837
CYP1A2	5.5	AC50	3162	nM	CHEMBL_ACT_6046825
USP2	5.4	Potency	3981	nM	CHEMBL_ACT_4723702
DRD2	5.26	AC50	5479	nM	CHEMBL_ACT_25140977
CYP1A2	5.2	AC50	6310	nM	CHEMBL_ACT_6055291
DRD3	5.15	AC50	7100	nM	CHEMBL_ACT_25194162
P08482	5.05	Potency	8912	nM	CHEMBL_ACT_4857940
ADRA2B	5	AC50	10000	nM	CHEMBL_ACT_25144331
CYP3A4	5	Potency	10000	nM	CHEMBL_ACT_5010318
CYP3A4	5	Potency	10000	nM	CHEMBL_ACT_5078732

Target pathways

Aggregated over 8 target gene(s): HTR1A, DRD2, DRD3, DRD4, ADRA1A, ADRA2A, ADRA2C, HTR2B.

Top Reactome pathways

23 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	5	ADRA1A, ADRA2A, ADRA2C, HTR1A, HTR2B
Signaling by GPCR	5	ADRA1A, ADRA2A, ADRA2C, HTR1A, HTR2B
Class A/1 (Rhodopsin-like receptors)	5	ADRA1A, ADRA2A, ADRA2C, HTR1A, HTR2B
Amine ligand-binding receptors	5	ADRA1A, ADRA2A, ADRA2C, HTR1A, HTR2B
GPCR ligand binding	5	ADRA1A, ADRA2A, ADRA2C, HTR1A, HTR2B
GPCR downstream signalling	4	ADRA1A, ADRA2A, ADRA2C, HTR2B
G alpha (i) signalling events	4	ADRA2A, ADRA2C, DRD3, DRD4
Dopamine receptors	3	DRD2, DRD3, DRD4
Adrenoceptors	3	ADRA1A, ADRA2A, ADRA2C
Hemostasis	2	ADRA2A, ADRA2C
Metabolism	2	ADRA2A, ADRA2C
Integration of energy metabolism	2	ADRA2A, ADRA2C
Serotonin receptors	2	HTR1A, HTR2B
Adrenaline signalling through Alpha-2 adrenergic receptor	2	ADRA2A, ADRA2C
Metabolism of proteins	2	ADRA2A, ADRA2C
Adrenaline,noradrenaline inhibits insulin secretion	2	ADRA2A, ADRA2C
G alpha (q) signalling events	2	ADRA1A, HTR2B
G alpha (z) signalling events	2	ADRA2A, ADRA2C
Regulation of insulin secretion	2	ADRA2A, ADRA2C
Surfactant metabolism	2	ADRA2A, ADRA2C
Platelet activation, signaling and aggregation	2	ADRA2A, ADRA2C
Platelet Aggregation (Plug Formation)	2	ADRA2A, ADRA2C
G alpha (12/13) signalling events	1	ADRA1A

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	8
signal transduction	8
regulation of vasoconstriction	4
intracellular calcium ion homeostasis	4
response to xenobiotic stimulus	4
positive regulation of MAPK cascade	4
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	3
chemical synaptic transmission	3
positive regulation of cell population proliferation	3
adult behavior	3
G protein-coupled serotonin receptor signaling pathway	3
adenylate cyclase-inhibiting dopamine receptor signaling pathway	3
response to histamine	3
response to morphine	3
negative regulation of insulin secretion	3

Indications & clinical

Indications

1 indication (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
Parkinson disease	4	MONDO:0005180	MONDO:0005180

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
Not specified	4
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01007864	PHASE3	COMPLETED	Influence of Piribedil (Clarium®) on Vigilance and Cognitive Function in Patients With Parkinson’s Disease Compared to Other Non-Ergot Dopamine Agonists
NCT00591994	Not specified	COMPLETED	Tinnitus Treatment With Piribedil Guided by Acoustic Otoemissions and Electrocochleography
NCT00725478	Not specified	COMPLETED	SEDPARK1: Safety and Efficacy Study With the Non-ergot Dopamine-agonist Piribedil in Parkinson’s Disease
NCT00727727	Not specified	COMPLETED	SEDPARK2: Post Marketing Surveillance to Observe Safety and Efficacy of Piribedil in Parkinson’s Disease (PIR-002/K)
NCT01519856	Not specified	COMPLETED	PIRLONG-PD Safety and Efficacy of Piribedil in Parkinson’s Disease During Long Term Therapy

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

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

Molecule	Source	Status	Shared targets
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
Pyrazinamide	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
APOMORPHINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
CABERGOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
DOXEPIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
EBASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
ILOPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
IPRINDOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
LOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
MIANSERIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
NEFAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
PERGOLIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
PIMOZIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
PROMAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
PROMETHAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
QUETIAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
REMOXIPRIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
RISPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
ROTIGOTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
SERTINDOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
SILODOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
SUNITINIB	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
THIORIDAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
THIOTHIXENE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
TRAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
VILAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
LISURIDE	ChEMBL	Phase 3	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
NEMONAPRIDE	ChEMBL	Phase 2	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
SPIPERONE	ChEMBL	Phase 2	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
SPIRAMIDE	ChEMBL	Phase 2	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
ZOTEPINE	ChEMBL	Phase 2	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
Fidaxomicin	PubChem	Approved	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, DRD4, HTR1A, HTR2B
chenodiol	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, HTR1A, HTR2B
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, HTR1A, HTR2B
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, HTR1A, HTR2B
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, HTR1A, HTR2B
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, HTR1A, HTR2B
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, HTR1A, HTR2B
BROMPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA2A, ADRA2C, DRD2, DRD3, HTR1A, HTR2B