View source for Piribedil

{{Short description|Dopamine agonist medication}}
{{Use dmy dates|date=March 2024}}
{{More citations needed|date=March 2025}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 414329835
| IUPAC_name = 2-[4-(benzo[1,3]dioxol-5-ylmethyl)piperazin-1-yl]pyrimidine
| image = Piribedil.svg
| width = 250
| alt = 
| image2 = Piribedil ball-and-stick model.png
| width2 = 
| alt2 = <!--Clinical data-->
| tradename = Pronoran, Trivastal Retard, Trastal, Trivastan, Clarium, others
| Drugs.com = {{drugs.com|international|piribedil}}
| pregnancy_category = 
| routes_of_administration = [[Oral administration|By mouth]]
| ATC_prefix = N04
| ATC_suffix = BC08
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | title = Active substance: piribedil | work = List of nationally authorised medicinal products | publisher = European Medicines Agency | date = 26 November 2020 | url = https://www.ema.europa.eu/documents/psusa/piribedil-list-nationally-authorised-medicinal-products-psusa/00002436/202003_en.pdf }}</ref>
| legal_status = Rx-only

<!--Pharmacokinetic data-->
| bioavailability = 10% (peak at 1 hour) {{Citation needed|date=June 2025}}
| protein_bound = 70–80% {{Citation needed|date=June 2025}}
| metabolism = extensive liver {{Citation needed|date=June 2025}}
| elimination_half-life = 1.7–6.9 hours {{Citation needed|date=June 2025}}
| excretion = [[Kidney]] (68%) and bile duct (25%) {{Citation needed|date=June 2025}}

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 3605-01-4
| PubChem = 4850
| IUPHAR_ligand = 49
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = DO22K1PRDJ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07305
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1371770
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 4684
| synonyms = <!--Chemical data-->
| C = 16
| H = 18
| N = 4
| O = 2
| SMILES = C1CN(CCN1CC2=CC3=C(C=C2)OCO3)C4=NC=CC=N4
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = OQDPVLVUJFGPGQ-UHFFFAOYSA-N
}}

'''Piribedil''' is an [[Management of Parkinson's disease#Medication|antiparkinsonian agent]] and [[piperazine]] [[derivative (chemistry)|derivative]] which acts as a [[D2 receptor|D<sub>2</sub>]] and [[D3 receptor|D<sub>3</sub> receptor]] [[agonist]]. It also has [[α2-adrenergic receptor|α<sub>2</sub>-adrenergic antagonist]] properties.<ref name="pmid11356907">{{cite journal | vauthors = Millan MJ, Cussac D, Milligan G, Carr C, Audinot V, Gobert A, Lejeune F, Rivet JM, Brocco M, Duqueyroix D, Nicolas JP, Boutin JA, Newman-Tancredi A | display-authors = 6 | title = Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 297 | issue = 3 | pages = 876–887 | date = June 2001 | pmid = 11356907 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11356907 }}</ref><ref name="pmid12649387">{{cite journal | vauthors = Gobert A, Di Cara B, Cistarelli L, Millan MJ | title = 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 | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 305 | issue = 1 | pages = 338–346 | date = April 2003 | pmid = 12649387 | doi = 10.1124/jpet.102.046383 | s2cid = 29234876 }}</ref>

{{TOC limit|3}}

==Medical uses==
* Treatment of [[Parkinson's disease]] (PD), either as [[monotherapy]] (without [[levodopa]]) or in combination with <small>L</small>-DOPA therapy, in the early stages of the disease as well as in the advanced ones{{Citation needed|date=March 2025}}
* Treatment of [[pathological]] [[cognitive deficit]]s in the [[elderly]] (impaired [[attention]], [[motivation]], [[memory]], etc.){{Citation needed|date=March 2025}}
* Treatment of [[dizziness]] in the young patients{{Citation needed|date=March 2025}}
* Treatment of [[retina]]l [[ischemic]] manifestations{{Citation needed|date=March 2025}}
* Adjunctive treatment of [[intermittent claudication]] due to [[peripheral vascular disease]] (PVD) of the [[lower limb]]s (stage 2){{Citation needed|date=March 2025}}
* Adjunctive treatment of [[anhedonia]], [[apathy]] and [[treatment-resistant depression]] in [[major depressive disorder|unipolar]] and [[bipolar disorder|bipolar]] depressives (''[[Off-label use|off-label]]''){{Citation needed|date=March 2025}}
* Treatment of [[Gait abnormality|gait disorders]] associated with Parkinson's disease (no related cause) and other forms of parkinsonism{{Citation needed|date=March 2025}}

===Other uses===
The drug has been shown to enhance working memory capacities in normal aging adults.<ref>{{cite journal | vauthors = Gierski F, Peretti CS, Ergis AM | title = Effects of the dopamine agonist piribedil on prefrontal temporal cortical network function in normal aging as assessed by verbal fluency | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 31 | issue = 1 | pages = 262–268 | date = January 2007 | pmid = 16876301 | doi = 10.1016/j.pnpbp.2006.06.017 | s2cid = 792757 }}</ref>

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.<ref>{{cite journal | vauthors = Bochkarev VK, Faĭzulloev AZ, Avedisova AS | title = [Efficacy of pronoran in age-related memory impairment] | journal = Zhurnal Nevrologii I Psikhiatrii imeni S.S. Korsakova | volume = 105 | issue = 2 | pages = 46–50 | year = 2005 | pmid = 15792142 }}</ref>

It enhances cognitive skill learning in healthy older adults.<ref>{{cite journal | vauthors = Peretti CS, Gierski F, Harrois S | title = Cognitive skill learning in healthy older adults after 2 months of double-blind treatment with piribedil | journal = Psychopharmacology | volume = 176 | issue = 2 | pages = 175–181 | date = November 2004 | pmid = 15138753 | doi = 10.1007/s00213-004-1869-8 | s2cid = 24952829 }}<!-- Service de Psychiatrie des Adultes, Hôpital Robert Debré, CHU de Reims, Avenue du Général Koenig, 51092, Reims Cedex, France. cperetti@chu-reims.fr --></ref>

It showed a positive effect in [[restless legs syndrome]].<ref>{{cite journal | vauthors = Evidente VG | title = Piribedil for restless legs syndrome: a pilot study | journal = Movement Disorders | volume = 16 | issue = 3 | pages = 579–581 | date = May 2001 | pmid = 11391766 | doi = 10.1002/mds.1104 | s2cid = 39995329 }}</ref>

==Side effects==
* Minor [[gastrointestinal]] upset ([[nausea]], [[vomiting]], [[flatulence]], etc.) in predisposed individuals, or when taken between meals: adjust dosage individually, and/or add [[domperidone]]{{Citation needed|date=March 2025}}
* [[Orthostatic hypotension]] or [[drowsiness]] may occur, particularly in predisposed individuals (underlying condition or causative illness){{Citation needed|date=March 2025}}
* Mild [[dizziness]], confusion and feeling "drunk" also may occur{{Citation needed|date=March 2025}}

As with other dopamine agonists (like [[pramipexole]] and [[ropinirole]]), compulsive behavior like [[Problem gambling|pathological gambling]], overeating, [[Oniomania|excessive shopping]], increased [[libido]], sexual and/or other intense urges, may develop.<ref>{{cite journal | vauthors = Tschopp L, Salazar Z, Gomez Botello MT, Roca CU, Micheli F | title = Impulse control disorder and piribedil: report of 5 cases | journal = Clinical Neuropharmacology | volume = 33 | issue = 1 | pages = 11–13 | year = 2010 | pmid = 19959959 | doi = 10.1097/WNF.0b013e3181c4ae2e | s2cid = 30844295 }}</ref><ref name="PI">TRIVASTAL Retard 50 (piribedil) Prescribing Information, Servier Laboratories, April 2008. [http://servier.com/sites/default/files/SPC_Trivastal.pdf] {{Webarchive|url=https://web.archive.org/web/20160809143507/http://www.servier.com/sites/default/files/SPC_Trivastal.pdf|date=9 August 2016}}</ref>

Another rare side effect of piribedil is excessive daytime sleepiness and unintended sleep episodes.<ref name="PI" /><ref>{{cite journal | vauthors = Gouraud A, Millaret A, Descotes J, Vial T | title = Piribedil-induced sleep attacks in patients without Parkinson disease: a case series | journal = Clinical Neuropharmacology | volume = 34 | issue = 3 | pages = 104–107 | year = 2011 | pmid = 21586915 | doi = 10.1097/WNF.0b013e31821f0d8b | s2cid = 22169346 }}</ref>

==Overdose==
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.{{medcn|date=January 2024}}

== Interactions ==

[[Dopamine antagonist]]s reduce the effect of piribedil.{{medcn|date=January 2024}}

==Pharmacology==

===Pharmacodynamics===
* [[Dopamine receptor]] agonist, selective for subtypes D<sub>2</sub> and D<sub>3</sub>{{Citation needed|date=March 2025}}
* Dopamine receptor antagonist, selective for subtypes D<sub>4</sub>.<ref name="pmid10989267">{{cite journal | vauthors = Arnsten AF, Murphy B, Merchant K | title = The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys | journal = Neuropsychopharmacology | volume = 23 | issue = 4 | pages = 405–10 | date = October 2000 | pmid = 10989267 | doi = 10.1016/S0893-133X(00)00133-0 | s2cid = 16143246 | doi-access = free }}</ref><ref name="pmid11532743">{{cite journal | vauthors = Nagaraja D, Jayashree S | title = Randomized study of the dopamine receptor agonist piribedil in the treatment of mild cognitive impairment | journal = The American Journal of Psychiatry | volume = 158 | issue = 9 | pages = 1517–9 | date = September 2001 | pmid = 11532743 | doi = 10.1176/appi.ajp.158.9.1517 }}</ref><ref name="39875/1021571">{{cite journal | vauthors = Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, Millan MJ | title = Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 303 | issue = 2 | pages = 805–814 | date = November 2002 | pmid = 12388667 | doi = 10.1124/jpet.102.039875 | s2cid = 35238120 }}</ref>
* [[Adrenergic receptor]] antagonist, subtypes α<sub>2A</sub> and α<sub>2C</sub>.<ref name="Zsilavecz">{{cite news|title=Piribedil| vauthors = Schubert-Zsilavecz M |work=Neue Arzneimittel 2008|language=de}}</ref>
* Lack of affinity to [[serotonin receptor]] 5-HT<sub>2B</sub>.<ref name="Zsilavecz" />

== References ==
{{Reflist}}

{{Antiparkinson}}
{{Hallucinogens}}
{{Adrenergic receptor modulators}}
{{Dopamine receptor modulators}}
{{Piperazines}}
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[[Category:Alpha-2 blockers]]
[[Category:Aminopyrimidines]]
[[Category:Benzodioxoles]]
[[Category:Benzylpiperazines]]
[[Category:Dopamine agonists]]
[[Category:1-(2-Pyrimidinyl)piperazines]]