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 =
| tradename = Pronoran, Trivastal Retard, Trastal, Trivastan, Clarium, others
| Drugs.com = {{drugs.com|international|piribedil}}
| pregnancy_category =
| routes_of_administration = By mouth
| ATC_prefix = N04
| ATC_suffix = BC08
| legal_EU = Rx-only
| legal_status = Rx-only
| bioavailability = 10% (peak at 1 hour)
| protein_bound = 70–80%
| metabolism = extensive liver
| elimination_half-life = 1.7–6.9 hours
| excretion = Kidney (68%) and bile duct (25%)
| 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 =
| 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 antiparkinsonian agent and piperazine derivative which acts as a D2 and D3 receptor agonist. It also has α2-adrenergic antagonist properties.{{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 }}{{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 }}
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Medical uses
- Treatment of Parkinson's disease (PD), either as monotherapy (without levodopa) or in combination with L-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 deficits 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 retinal ischemic manifestations{{Citation needed|date=March 2025}}
- Adjunctive treatment of intermittent claudication due to peripheral vascular disease (PVD) of the lower limbs (stage 2){{Citation needed|date=March 2025}}
- Adjunctive treatment of anhedonia, apathy and treatment-resistant depression in unipolar and bipolar depressives (off-label){{Citation needed|date=March 2025}}
- Treatment of 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.{{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 }}
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.{{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 }}
It enhances cognitive skill learning in healthy older adults.{{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 }}
It showed a positive effect in restless legs syndrome.{{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 }}
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 pathological gambling, overeating, excessive shopping, increased libido, sexual and/or other intense urges, may develop.{{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 }}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/20121219062430/http://www.servier.com/sites/default/files/SPC_Trivastal.pdf|date=19 December 2012}}
Another rare side effect of piribedil is excessive daytime sleepiness and unintended sleep episodes.{{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 }}
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 antagonists reduce the effect of piribedil.{{medcn|date=January 2024}}
Pharmacology
=Pharmacodynamics=
- Dopamine receptor agonist, selective for subtypes D2 and D3{{Citation needed|date=March 2025}}
- Dopamine receptor antagonist, selective for subtypes D4.{{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 }}{{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 }}{{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 }}
- Adrenergic receptor antagonist, subtypes α2A and α2C.{{cite news|title=Piribedil| vauthors = Schubert-Zsilavecz M |work=Neue Arzneimittel 2008|language=de}}
- Lack of affinity to serotonin receptor 5-HT2B.
References
{{Reflist}}
{{Antiparkinson}}
{{Hallucinogens}}
{{Adrenergic receptor modulators}}
{{Dopamine receptor modulators}}
{{Piperazines}}
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