Piribedil

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Piribedil
Piribedil.svg
Systematic (IUPAC) name
2-[4-(benzo[1,3]dioxol-5-ylmethyl)piperazin-1-yl]pyrimidine
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
  • Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 10% (peak at 1 hour)
Protein binding 70–80%
Metabolism extensive hepatic
Half-life 1.7–6.9 hours
Excretion Renal (68%) and biliary (25%)
Identifiers
CAS number 3605-01-4 YesY
ATC code N04BC08
PubChem CID 4850
IUPHAR ligand 49
ChemSpider 4684 N
UNII DO22K1PRDJ N
KEGG D07305 YesY
ChEMBL CHEMBL1371770 N
Chemical data
Formula C16H18N4O2 
Mol. mass 298.340 g/mol
 N (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.[1][2]

Indications[edit]

Other uses[edit]

The drug has been shown to enhance working memory capacities in normal aging adults.[3]

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.[4]

It enhances cognitive skill learning in healthy older adults.[5]

It showed a positive effect in restless legs syndrome.[6]

Dosage[edit]

Parkinson's disease[edit]

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[edit]

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

Adverse effects[edit]

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.[7][8]

Another rare side effect of piribedil is excessive daytime sleepiness and unintended sleep episodes.[9][8]

Interactions[edit]

Dopamine antagonists reduce the effect of piribedil.

Overdose[edit]

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.

Receptor affinities[edit]

See also[edit]

  • Piribedil structure components:

References[edit]

  1. ^ 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. 
  2. ^ Gobert A, Di Cara B, Cistarelli L, Millan MJ (April 2003). "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". The Journal of Pharmacology and Experimental Therapeutics 305 (1): 338–46. doi:10.1124/jpet.102.046383. PMID 12649387. 
  3. ^ 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.  edit
  4. ^ 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 / Ministerstvo zdravookhraneniia i meditsinskoi promyshlennosti Rossiiskoi Federatsii, Vserossiiskoe obshchestvo nevrologov [i] Vserossiiskoe obshchestvo psikhiatrov 105 (2): 46–50. PMID 15792142.  edit
  5. ^ 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.  edit
  6. ^ Evidente, V. G. (May 2001). "Piribedil for restless legs syndrome: a pilot study". Movement disorders : official journal of the Movement Disorder Society 16 (3): 579–581. doi:10.1002/mds.1104. PMID 11391766.  edit
  7. ^ Tschopp L., Salazar Z. et al. (2010). "Impulse control disorder and piribedil: report of 5 cases.". Clin. Neuropharmacology 33 (1): 11—13. doi:10.1097/WNF.0b013e3181c4ae2e. PMID 19959959. 
  8. ^ a b TRIVASTAL® Retard 50 (piribedil) Prescribing Information, Servier Laboratories, April 2008. [1]
  9. ^ Gouraud A., Millaret A. et al. (2011). "Piribedil-induced sleep attacks in patients without Parkinson disease: a case series.". Clin. Neuropharmacology 34 (3): 104—107. doi:10.1097/WNF.0b013e31821f0d8b. PMID 21586915. 
  10. ^ Arnsten et al., 2000; Nagaraja and Jayashree, 2001. "Piribedil". 
  11. ^ 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". J. Pharmacol. Exp. Ther. 303 (2): 812. PMID 11356907. 
  12. ^ a b Schubert-Zsilavecz, M. "Piribedil". Neue Arzneimittel 2008 (in German).