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

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
Dopamine receptor stimulation in the treatment of depression: piribedil (ET-495).	1978	622219
DA agonists -- non-ergot derivatives: piribedil: management of Parkinson's disease.	2002	12211147
Choosing the right dopamine agonist for patients with Parkinson's disease.	2002	12201621
Sleep attacks in patients taking dopamine agonists: review.	2002 Jun 22	12077032
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.	2002 Nov	12388668
Repeated administration of piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: a behavioural and biochemical investigation.	2002 Sep	12360537
[Use of pronoran (piribedil) in Parkinson's disease: the results of a multicenter study].	2003	14681961
Efficacy and safety of piribedil in early combination with L-dopa in the treatment of Parkinson's disease: a 6-month open study.	2004 Nov	15825702
[Modern aproaches to the treatment of early stages of Parkinson disease].	2005	16329637
Chemically modified carbon paste electrode for the potentiometric flow injection analysis of piribedil in pharmaceutical preparation and urine.	2005 Jul 15	15967290
[Dopaminergic and noradrenergic therapy of cognitive impairment].	2006	17069060
The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.	2006 Apr	16267842
Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.	2006 Dec	17013922
Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats.	2006 Jun	16682961
Identification of amino acid determinants of dopamine 2 receptor synthetic agonist function.	2007 Apr	17204745
Blockage of dopaminergic D(2) receptors produces decrease of REM but not of slow wave sleep in rats after REM sleep deprivation.	2008 Apr 9	18201777
Tinnitus treatment with piribedil guided by electrocochleography and acoustic otoemissions.	2009 Aug	19574947
Parkinson's disease sleep scale, sleep logs, and actigraphy in the evaluation of sleep in parkinsonian patients.	2009 Sep	19404716

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.

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