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Piribedil ball-and-stick model.png
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
By mouth
ATC code
Legal status
Legal status
  • EU: Rx-only [1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability10% (peak at 1 hour)
Protein binding70–80%
Metabolismextensive liver
Elimination half-life1.7–6.9 hours
ExcretionKidney (68%) and bile duct (25%)
  • 2-[4-(benzo[1,3]dioxol-5-ylmethyl)piperazin-1-yl]pyrimidine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.020.695 Edit this at Wikidata
Chemical and physical data
Molar mass298.346 g·mol−1
3D model (JSmol)
  • C1CN(CCN1CC2=CC3=C(C=C2)OCO3)C4=NC=CC=N4
  • 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 ☒N
 ☒NcheckY (what is this?)  (verify)

Piribedil (trade names Pronoran, Trivastal Retard, Trastal, Trivastan, Clarium and others) is an antiparkinsonian agent and piperazine derivative which acts as a D2 and D3 receptor agonist. It also has α2-adrenergic antagonist properties.[2][3]

Medical uses

Other uses

The drug has been shown to enhance working memory capacities in normal aging adults.[4]

In age-related memory impairment, it has a positive effect on psychophysiological state of elderly people, improving memory and attention and increasing the velocity of psychomotor reactions and lability of nervous processes.[5]

It enhances cognitive skill learning in healthy older adults.[6]

It showed a positive effect in restless legs syndrome.[7]


Parkinson's disease

Administration of piribedil should be initiated with one sustained-release tablet (50 mg) daily during the first week. Dosage should then be gradually increased every week until achieving the optimal therapeutic dose:

  • As monotherapy: three to five tablets in three to five doses daily.
  • In combination with L-DOPA therapy: one to three tablets daily.

Other indications

One tablet daily at the end of the main meal. In severe cases: two tablets daily in two doses.

Side effects

As with other dopamine agonists (like pramipexole and ropinirole), compulsive behavior like pathological gambling, overeating, excessive shopping, increased libido, sexual and/or other intense urges, may develop.[8][9]

Another rare side effect of piribedil is excessive daytime sleepiness and unintended sleep episodes.[9][10]


At very high doses, piribedil has an emetic action on the chemoreceptor trigger zone (CTZ). Tablets will thus be rapidly rejected, which explains why no data are currently available concerning the risk of overdosage.


Dopamine antagonists reduce the effect of piribedil.




Parkinson's patent:[14]

Synthesis:[15] Patent:[16] 97% yield:[17] China patent:[18] Purification:[19] Sino Sino2

2-Chloropyrimidine [1722-12-9] (1) and 1-Piperonylpiperazine [32231-06-4] (2) give Piribedil (3). Alternately, 2-(1-Piperazinyl)pyrimidine [20980-22-7] (4) can be reacted with Piperonyl bromide [2606-51-1] (5).


  1. ^ https://www.ema.europa.eu/documents/psusa/piribedil-list-nationally-authorised-medicinal-products-psusa/00002436/202003_en.pdf[bare URL PDF]
  2. ^ Millan MJ, Cussac D, Milligan G, et al. (June 2001). "Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization". The Journal of Pharmacology and Experimental Therapeutics. 297 (3): 876–87. PMID 11356907.
  3. ^ Gobert A, Di Cara B, Cistarelli L, Millan MJ (April 2003). "Piribedil enhances frontocortical and hippocampal release of epinephrine in freely moving rats by blockade of alpha 2A-adrenoceptors: a dialysis comparison to talipexole and quinelorane in the absence of acetylcholinesterase inhibitors". The Journal of Pharmacology and Experimental Therapeutics. 305 (1): 338–46. doi:10.1124/jpet.102.046383. PMID 12649387. S2CID 29234876.
  4. ^ Gierski, F.; Peretti, C.; Ergis, A. (30 January 2007). "Effects of the dopamine agonist piribedil on prefrontal temporal cortical network function in normal aging as assessed by verbal fluency". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 31 (1): 262–268. doi:10.1016/j.pnpbp.2006.06.017. PMID 16876301. S2CID 792757.
  5. ^ Bochkarev, V. K.; Faĭzulloev, A. Z.; Avedisova, A. S. (2005). "Efficacy of pronoran in age-related memory impairment". Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova. 105 (2): 46–50. PMID 15792142.
  6. ^ Peretti, C. S.; Gierski, F.; Harrois, S. (November 2004). "Cognitive skill learning in healthy older adults after 2 months of double-blind treatment with piribedil". Psychopharmacology. 176 (2): 176–182. doi:10.1007/s00213-004-1869-8. PMID 15138753. S2CID 24952829.
  7. ^ Evidente, V. G. (May 2001). "Piribedil for restless legs syndrome: a pilot study". Movement Disorders. 16 (3): 579–581. doi:10.1002/mds.1104. PMID 11391766. S2CID 39995329.
  8. ^ Tschopp L.; Salazar Z.; et al. (2010). "Impulse control disorder and piribedil: report of 5 cases". Clin. Neuropharmacol. 33 (1): 11–13. doi:10.1097/WNF.0b013e3181c4ae2e. PMID 19959959. S2CID 30844295.
  9. ^ a b TRIVASTAL Retard 50 (piribedil) Prescribing Information, Servier Laboratories, April 2008. [1] Archived 2012-12-19 at the Wayback Machine
  10. ^ Gouraud A.; Millaret A.; et al. (2011). "Piribedil-induced sleep attacks in patients without Parkinson disease: a case series". Clin. Neuropharmacol. 34 (3): 104–107. doi:10.1097/WNF.0b013e31821f0d8b. PMID 21586915. S2CID 22169346.
  11. ^ Arnsten et al., 2000; Nagaraja and Jayashree, 2001. "Piribedil".{{cite news}}: CS1 maint: multiple names: authors list (link)
  12. ^ ADRIAN NEWMAN-TANCREDI, DIDIER CUSSAC, VALE´ RIE AUDINOT, JEAN-PAUL NICOLAS, FRE´ DE´ RIC DE CEUNINCK, JEAN-A. BOUTIN, and MARK J. MILLAN (June 2002). "Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. II. Agonist and Antagonist Properties at Subtypes of Dopamine D2-Like Receptor and α1/α2-Adrenoceptor" (PDF). J. Pharmacol. Exp. Ther. 303 (2): 805–14. doi:10.1124/jpet.102.039875. PMID 12388667. S2CID 35238120.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ a b Schubert-Zsilavecz, M. "Piribedil". Neue Arzneimittel 2008 (in German).
  14. ^ H Corrodi & K Fuxe, U.S. Patent 3,737,541 (1973 to Science Union et Cie).
  15. ^ Regnier, Gilbert; Canevari, R. J.; Laubie, M. J.; Le Douarec, J. C. (1968). "Synthesis and vasodilator activity of new piperazine derivatives". Journal of Medicinal Chemistry. 11 (6): 1151–1155. doi:10.1021/jm00312a010.
  16. ^ Regnier Gilbert, Canevari Roger, & Laubie Michel, U.S. Patent 3,299,067 (1967 to Science Union et Cie).
  17. ^ Pei Shan, Siah; Dang, Tuan Thanh; Seayad, Abdul Majeed; Ramalingam, Balamurugan (2014). "Reusable Supported Ruthenium Catalysts for the Alkylation of Amines by using Primary Alcohols". ChemCatChem. 6 (3): 808–814. doi:10.1002/cctc.201300971.
  18. ^ Kang Yanlong, CN 1884280  (2006 to BEIJING D-VENTURE PHARM T CORP).
  19. ^ Shean-Jeng Jong & Yu-Sheng Lin, U.S. Patent 7,241,891 (2005 to National Chung Shan Institute of Science and Technology NCSIST).

External links

  • "Piribedil". Drug Information Portal. U.S. National Library of Medicine.