Piribedil Explained

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]}

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
• Treatment of pathological cognitive deficits in the elderly (impaired attention, motivation, memory, etc.)
• Treatment of dizziness in the young patients
• Treatment of retinal ischemic manifestations
• Adjunctive treatment of intermittent claudication due to peripheral vascular disease (PVD) of the lower limbs (stage 2)
• Adjunctive treatment of anhedonia, apathy and treatment-resistant depression in unipolar and bipolar depressives (off label)
• Treatment of gait disorders associated with Parkinson's disease (no related cause) and other forms of parkinsonism

Other uses

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]

Side effects

• Minor gastrointestinal upset (nausea, vomiting, flatulence, etc.) in predisposed individuals, or when taken between meals: adjust dosage individually, and/or add domperidone;
• Orthostatic hypotension or drowsiness may occur, particularly in predisposed individuals (underlying condition or causative illness);
• Mild dizziness, confusion and feeling "drunk" also may occur.

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]

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.

Interactions

Dopamine antagonists reduce the effect of piribedil.

Pharmacology

Pharmacodynamics

• Dopamine receptor agonist, selective for subtypes D₂ and D₃.
• Dopamine receptor antagonist, selective for subtypes D₄.^{[10] [11] [12]}
• Adrenergic receptor antagonist, subtypes α_2A and α_2C.^[13]
• Lack of affinity to serotonin receptor 5-HT_2B.

Notes and References

1. 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 . 6 . 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 . 876–887 . June 2001 . 11356907 .
2. Gobert A, Di Cara B, Cistarelli L, Millan MJ . 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 . 338–346 . April 2003 . 12649387 . 10.1124/jpet.102.046383 . 29234876 .
3. Gierski F, Peretti CS, Ergis AM . Effects of the dopamine agonist piribedil on prefrontal temporal cortical network function in normal aging as assessed by verbal fluency . Progress in Neuro-Psychopharmacology & Biological Psychiatry . 31 . 1 . 262–268 . January 2007 . 16876301 . 10.1016/j.pnpbp.2006.06.017 . 792757 .
4. Bochkarev VK, Faĭzulloev AZ, Avedisova AS . [Efficacy of pronoran in age-related memory impairment] . Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova . 105 . 2 . 46–50 . 2005 . 15792142 .
5. Peretti CS, Gierski F, Harrois S . Cognitive skill learning in healthy older adults after 2 months of double-blind treatment with piribedil . Psychopharmacology . 176 . 2 . 175–181 . November 2004 . 15138753 . 10.1007/s00213-004-1869-8 . 24952829 .
6. Evidente VG . Piribedil for restless legs syndrome: a pilot study . Movement Disorders . 16 . 3 . 579–581 . May 2001 . 11391766 . 10.1002/mds.1104 . 39995329 .
7. Tschopp L, Salazar Z, Gomez Botello MT, Roca CU, Micheli F . Impulse control disorder and piribedil: report of 5 cases . Clinical Neuropharmacology . 33 . 1 . 11–13 . 2010 . 19959959 . 10.1097/WNF.0b013e3181c4ae2e . 30844295 .
8. TRIVASTAL Retard 50 (piribedil) Prescribing Information, Servier Laboratories, April 2008. http://servier.com/sites/default/files/SPC_Trivastal.pdf
9. Gouraud A, Millaret A, Descotes J, Vial T . Piribedil-induced sleep attacks in patients without Parkinson disease: a case series . Clinical Neuropharmacology . 34 . 3 . 104–107 . 2011 . 21586915 . 10.1097/WNF.0b013e31821f0d8b . 22169346 .
10. Arnsten AF, Murphy B, Merchant K . The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys . Neuropsychopharmacology . 23 . 4 . 405–10 . October 2000 . 10989267 . 10.1016/S0893-133X(00)00133-0 . 16143246 . free .
11. Nagaraja D, Jayashree S . Randomized study of the dopamine receptor agonist piribedil in the treatment of mild cognitive impairment . The American Journal of Psychiatry . 158 . 9 . 1517–9 . September 2001 . 11532743 . 10.1176/appi.ajp.158.9.1517 .
12. Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, Millan MJ . 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 . The Journal of Pharmacology and Experimental Therapeutics . 303 . 2 . 805–814 . November 2002 . 12388667 . 10.1124/jpet.102.039875 . 35238120 .
13. News: Piribedil. Schubert-Zsilavecz M . Neue Arzneimittel 2008. de.