PIRIBEDIL MESYLATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H18N4O2.CH4O3S
Molecular Weight	394.445
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=DEZKFCIOSKCCHK-UHFFFAOYSA-N

InChI=1S/C16H18N4O2.CH4O3S/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;1-5(2,3)4/h1-5,10H,6-9,11-12H2;1H3,(H,2,3,4)

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

Molecular Formula	CH4O3S
Molecular Weight	96.106
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
Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome.	2010-12-29	21190576
Pre-treatment with dopamine agonists influence L-dopa mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat.	2010-11-12	20434491
From the cell to the clinic: a comparative review of the partial D₂/D₃receptor agonist and α2-adrenoceptor antagonist, piribedil, in the treatment of Parkinson's disease.	2010-11	20600305
Delusional infestation induced by piribedil add-on in Parkinson's disease.	2010-08	20614418
Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.	2010-02-15	20063435
Cognitive psychiatry in India.	2010-01	21836668
Is there an inhibitory-response-control system in the rat? Evidence from anatomical and pharmacological studies of behavioral inhibition.	2010-01	19615404
Impulse control disorder and piribedil: report of 5 cases.	2009-12-05	19959959
Parkinson's disease sleep scale, sleep logs, and actigraphy in the evaluation of sleep in parkinsonian patients.	2009-09	19404716
Tinnitus treatment with piribedil guided by electrocochleography and acoustic otoemissions.	2009-08	19574947
Hallucinations: Etiology and clinical implications.	2009-07	21180490
Dopamine Agonists and their risk to induce psychotic episodes in Parkinson's disease: a case-control study.	2009-06-10	19515253
Ruthenium-catalyzed N-alkylation of amines and sulfonamides using borrowing hydrogen methodology.	2009-02-11	19191700
Mild cognitive impairment: The dilemma.	2009-01	21416016
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.	2008-09	19506724
Current management of the cognitive dysfunction in Parkinson's disease: how far have we come?	2008-08	18535172
Comparative effects of the dopaminergic agonists piribedil and bromocriptine in three different memory paradigms in rodents.	2008-07	18308794
Blockage of dopaminergic D(2) receptors produces decrease of REM but not of slow wave sleep in rats after REM sleep deprivation.	2008-04-09	18201777
[Implication of piribedil (pronoran) in the treatment of Parkinson's disease; a clinical and pharmacoeconomic analysis].	2008	18567194
Impact of newer pharmacological treatments on quality of life in patients with Parkinson's disease.	2008	18547126
Peripheral edema and dopamine agonists in Parkinson disease.	2007-10	17923645
Identification of amino acid determinants of dopamine 2 receptor synthetic agonist function.	2007-04	17204745
Genetic Contribution of Catechol-O-methyltransferase Polymorphism in Patients with Migraine without Aura.	2007-03	19513339
About the anti-Parkinson equivalency of levodopa and dopamine agonists.	2007-02-03	17272974
Impaired cognition and attention in adults: pharmacological management strategies.	2007-02	19300541
Effects of the dopamine agonist piribedil on prefrontal temporal cortical network function in normal aging as assessed by verbal fluency.	2007-01-30	16876301
A reversed-phase high-performance liquid chromatographic method for the determination of zafirlukast in pharmaceutical formulations and human plasma.	2007-01-18	17225602
[Cognitive disturbances and dysfunction of neuromediator systems in cerebral vascular insufficiency after treatment with pronoran].	2007	18689025
Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives.	2007	18019829
[Effect of dopamine deficiency on the preparation of visually guided saccadic eye movements].	2006-12-07	17147199
Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.	2006-12	17013922
Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors.	2006-11	17021388
The dopamine agonist piribedil with L-DOPA improves attentional dysfunction: relevance for Parkinson's disease.	2006-11	16920993
Prevalence and costs of parkinsonian syndromes associated with orthostatic hypotension.	2006-08-05	16886700
Switching from levodopa to the long-acting dopamine D2/D3 agonist piribedil reduces the expression of dyskinesia while maintaining effective motor activity in MPTP-treated primates.	2006-06-15	16772809
Restless legs syndrome: diagnosis and review of management options.	2006-06	19412460
Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats.	2006-06	16682961
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.	2006-04	16267842
Enhancement in dissolution pattern of piribedil by molecular encapsulation with beta-cyclodextrin.	2006-03	16636717
Proposed dose equivalence for rapid switch between dopamine receptor agonists in Parkinson's disease: a review of the literature.	2006-01	16490575
Pathophysiology and management of syncope in Kearns-Sayre syndrome.	2006	17086014
[Dopaminergic and noradrenergic therapy of cognitive impairment].	2006	17069060
[The role of pronoran in the therapy of late stage of Parkinson's disease].	2006	16737158
Pharmacokinetic optimisation in the treatment of Parkinson's disease : an update.	2006	16485914
[Modern aproaches to the treatment of early stages of Parkinson disease].	2005	16329637
Drug treatment of Parkinson's disease.	2004-09	22033779
Age-related mild cognitive deficit: a ready-to-use concept?	2003-03	22033646
Dopamine receptor stimulation in the treatment of depression: piribedil (ET-495).	1978	622219
A comparison of piribedil, procyclidine and placebo in the control of phenothiazine-induced parkinsonism.	1977-06	326325
Piribedil: its synergistic effect in multidrug regimens for parkinsonism.	1976-05	944394

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 18:08:37 GMT 2025` Edited by `admin` on `Mon Mar 31 18:08:37 GMT 2025`
Record UNII	1U37NGM6KK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIRIBEDIL MONOMETHANESULFONATE

Preferred Name

English

PIRIBEDIL MESYLATE

Common Name

English

PIRIBEDIL MONOMETHYLSULFONATE

Common Name

English

2-(4-(1,3-BENZODIOXOL-5-YLMETHYL)PIPERAZIN-1-YL)PYRIMIDINE, METHANESULFONIC ACID

Common Name

English

ET-495 METHANESULFONATE

Common Name

English

Piribedil monomethanesulfonate [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

198284