PIRIBEDIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H18N4O2
Molecular Weight	298.3397
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C(N1CCN(CC1)C2=NC=CC=N2)C3=CC4=C(OCO4)C=C3

InChI

InChIKey=OQDPVLVUJFGPGQ-UHFFFAOYSA-N

InChI=1S/C16H18N4O2/c1-4-17-16(18-5-1)20-8-6-19(7-9-20)11-13-2-3-14-15(10-13)22-12-21-14/h1-5,10H,6-9,11-12H2

HIDE SMILES / InChI

Molecular Formula	C16H18N4O2
Molecular Weight	298.3397
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.servier.com.ve/sites/default/files/spc-pil/spc-trivastal.pdf | https://www.ncbi.nlm.nih.gov/pubmed/11222455

Piribedil is an antiparkinsonian agent which acts as D2 and D3 receptor agonist. In European countries and worldwide it is used as a monotherapy or in combination with dopatherapy for treatment of Parkinson's disease, cognitive impairment and obliterating arteriopathy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
D(3) dopamine receptor 16 Target ID: P35462 Gene ID: 1814.0 Gene Symbol: DRD3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11222455	Agonist 2752
D(2) dopamine receptor 58 Target ID: P14416 Gene ID: 1813.0 Gene Symbol: DRD2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8588823	Agonist 2752

Conditions

Condition	Modality	Highest Phase	Product
Chronic obliterating arteriopathy 2 Sources: http://www.servier.com.ve/sites/default/files/spc-pil/spc-trivastal.pdf	Primary	Approved 8583	TRIVASTAL Approved Use Adjunctive treatment of intermittent claudication in chronic obliterating arteriopathies of the lower limbs (in stage 2).
Cognitive impairment 15 Sources: http://www.servier.com.ve/sites/default/files/spc-pil/spc-trivastal.pdf	Palliative	Approved 8583	TRIVASTAL Approved Use Adjunctive symptomatic treatment of chronic pathological cognitive and neurosensorial deficit in elderly subjects (excluding Alzheimer's disease and other dementia).
Parkinson's disease 232 Sources: http://www.servier.com.ve/sites/default/files/spc-pil/spc-trivastal.pdf	Primary	Approved 8583	TRIVASTAL Approved Use Treatment of Parkinson's disease: either as monotherapy (treatment of forms with predominant tremor), or in association with dopatherapy from the outset, or secondarily, particularly in forms with tremor.

C_max

Value	Dose	Analyte	Population
350.91 ng/mL EXPERIMENT https://www.researchgate.net/publication/361801101_Simple_and_rapid_LC-MSMS_method_for_determination_of_Piribedil_in_human_plasma	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
23.2 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
46.5 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
86 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	8 mg single, intravenous dose: 8 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
222.3 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	16 mg single, intravenous dose: 16 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
4080 pg × h/mL EXPERIMENT https://www.researchgate.net/publication/361801101_Simple_and_rapid_LC-MSMS_method_for_determination_of_Piribedil_in_human_plasma	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
23.9 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
47.1 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
96.7 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	8 mg single, intravenous dose: 8 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
253.4 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	16 mg single, intravenous dose: 16 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
11.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	2 mg single, intravenous dose: 2 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	4 mg single, intravenous dose: 4 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	8 mg single, intravenous dose: 8 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
12.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15726579/	16 mg single, intravenous dose: 16 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PIRIBEDIL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
150 mg 2 times / day multiple, oral Highest studied dose Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17013922/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17013922/	Disc. AE: Gastrointestinal disorder, Psychiatric symptom... AEs leading to discontinuation/dose reduction: Gastrointestinal disorder (2.5%) Psychiatric symptom (1%) Sources: https://pubmed.ncbi.nlm.nih.gov/17013922/

AEs

AE	Significance	Dose	Population
Psychiatric symptom	1% Disc. AE	150 mg 2 times / day multiple, oral Highest studied dose Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17013922/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17013922/
Gastrointestinal disorder	2.5% Disc. AE	150 mg 2 times / day multiple, oral Highest studied dose Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17013922/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17013922/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	substrate 9

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153 MRP3 246 MRP4 290 CYP19A1 429 MRP2 499 BSEP 550	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNzE3NzAifX0=	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1NzQ4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNzE3NzAifX0=	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1OTE4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNzE3NzAifX0=	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNzE3NzAifX0=	no [IC50 >133 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4850#section=Biological-Test-Results Page: 155.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTM3MTc3MCJ9fQ==	yes [IC50 0.1995 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNzE3NzAifX0=	yes [IC50 0.631 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzNzE3NzAifX0=	yes [IC50 1.9953 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4850#section=Biological-Test-Results Page: 9.0	yes [IC50 10.964 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4850#section=Biological-Test-Results Page: 5.0	yes [IC50 2.4545 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4850#section=Biological-Test-Results Page: 11 \| 185	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	substrate 9 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/4850#section=Biological-Test-Results Page: 218.0

PubMed

Title	Date	PubMed
Piribedil: its synergistic effect in multidrug regimens for parkinsonism.	1976 May	944394
A comparison of piribedil, procyclidine and placebo in the control of phenothiazine-induced parkinsonism.	1977 Jun	326325
Sleep attacks and Parkinson's disease treatment.	2000 Apr 15	10776750
Discriminative stimulus properties of the dopamine D3 receptor agonists, PD128,907 and 7-OH-DPAT: a comparative characterization with novel ligands at D3 versus D2 receptors.	2000 Feb 14	10728880
Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization.	2001 Jun	11356907
Dopamine agonist-induced dyskinesias are correlated to both firing pattern and frequency alterations of pallidal neurones in the MPTP-treated monkey.	2001 Mar	11222455
Piribedil for restless legs syndrome: a pilot study.	2001 May	11391766
Formulation and in vitro-in vivo evaluation of piribedil solid lipid micro- and nanoparticles.	2001 May-Jun	11308226
[Use of dopamine agonists in the treatment of Parkinson's disease].	2002	12378886
[Alpha-2 adrenergic receptors and Parkinson's disease].	2002 Jul 27	12192732
Gateways to clinical trials.	2002 Jul-Aug	12224444
Repeated administration of piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: a behavioural and biochemical investigation.	2002 Sep	12360537
Efficacy of piribedil as early combination to levodopa in patients with stable Parkinson's disease: a 6-month, randomized, placebo-controlled study.	2003 Apr	12671949
Piribedil enhances frontocortical and hippocampal release of acetylcholine in freely moving rats by blockade of alpha 2A-adrenoceptors: a dialysis comparison to talipexole and quinelorane in the absence of acetylcholinesterase inhibitors.	2003 Apr	12649387
Electroanalytical characteristics of piribedil and its differential pulse and square wave voltammetric determination in pharmaceuticals and human serum.	2003 Mar 10	12615235
[Treatment of Parkinson's disease: use of piribedil].	2004	14870695
Acute treatment of migraine. Breaking the paradigm of monotherapy.	2004 Jan 28	15005810
Determination of piribedil in pharmaceutical formulations by micellar electrokinetic capillary chromatography.	2004 May	14985904
[Efficacy of pronoran in age-related memory impairment].	2005	15792142
Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.	2006 Dec	17013922
Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors.	2006 Nov	17021388
The dopamine agonist piribedil with L-DOPA improves attentional dysfunction: relevance for Parkinson's disease.	2006 Nov	16920993
A reversed-phase high-performance liquid chromatographic method for the determination of zafirlukast in pharmaceutical formulations and human plasma.	2006 Nov-Dec	17225602
[Effect of dopamine deficiency on the preparation of visually guided saccadic eye movements].	2006 Sep-Oct	17147199
Effects of the dopamine agonist piribedil on prefrontal temporal cortical network function in normal aging as assessed by verbal fluency.	2007 Jan 30	16876301
About the anti-Parkinson equivalency of levodopa and dopamine agonists.	2007 Jan-Feb	17272974
Peripheral edema and dopamine agonists in Parkinson disease.	2007 Oct	17923645
Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans.	2008 Sep	19506724
Mild cognitive impairment: The dilemma.	2009 Jan	21416016
Impulse control disorder and piribedil: report of 5 cases.	2010 Jan-Feb	19959959

Patents

Sample Use Guides

In Vivo Use Guide

For the treatment of Parkinson's disease as a monotherapy, piribedil should be administered orally at 150 to 250 mg.

Route of Administration: Oral

In Vitro Use Guide

Binding of piribedil to D2, D3 and D4 receptors was measured using [3H]spiperone as a radiolabel. Coronal sections from rat brains were cut at the level of the anterior caudate-putame. The sections were thaw-mounted on gelatin-coated glass slides. Sections were incubated for 5 min in a 50mM Tris-HCl buffer, then were incubated for 30 min at room temperature in the incubation buffer. Piribedil was tested in vitro at 5 different concentrations, from 10 uM to 1 nM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:45:05 GMT 2025` Edited by `admin` on `Mon Mar 31 17:45:05 GMT 2025`
Record UNII	DO22K1PRDJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRIVASTAL

Preferred Name

English

PIRIBEDIL

Official Name

English

Piribedil [WHO-DD]

Common Name

English

piribedil [INN]

Common Name

English

EU-4200

Code

English

2-(4-PIPERONYL-1-PIPERAZINYL)PYRIMIDINE

Systematic Name

English

ET-495

Code

English

PIRIBEDIL [MI]

Common Name

English

PIRIBEDIL [MART.]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N04BC08