Potency and safety analysis of hemp-derived delta-9 products: The hemp vs. cannabis demarcation problem
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| AHFS/Drugs.com | International Drug Names |
| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 10% (peak at 1 hour) |
| Protein binding | 70–80% |
| Metabolism | extensive liver |
| Elimination half-life | 1.7–6.9 hours |
| Excretion | Kidney (68%) and bile duct (25%) |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.020.695 |
| Chemical and physical data | |
| Formula | C16H18N4O2 |
| Molar mass | 298.346 g·mol−1 |
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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
- 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.[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]
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.[8][9]
Another rare side effect of piribedil is excessive daytime sleepiness and unintended sleep episodes.[9][10]
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.[medical citation needed]
Interactions
Dopamine antagonists reduce the effect of piribedil.[medical citation needed]
Pharmacology
Pharmacodynamics
- Dopamine receptor agonist, selective for subtypes D2 and D3.
- Dopamine receptor antagonist, selective for subtypes D4.[11][12][13]
- Adrenergic receptor antagonist, subtypes α2A and α2C.[14]
- Lack of affinity to serotonin receptor 5-HT2B.[14]
References
- ^ "Active substance: piribedil" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 26 November 2020.
- ^ Millan MJ, Cussac D, Milligan G, Carr C, Audinot V, Gobert A, 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): 876–887. PMID 11356907.
- ^ 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): 338–346. doi:10.1124/jpet.102.046383. PMID 12649387. S2CID 29234876.
- ^ Gierski F, Peretti CS, Ergis AM (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 & Biological Psychiatry. 31 (1): 262–268. doi:10.1016/j.pnpbp.2006.06.017. PMID 16876301. S2CID 792757.
- ^ Bochkarev VK, Faĭzulloev AZ, Avedisova AS (2005). "[Efficacy of pronoran in age-related memory impairment]". Zhurnal Nevrologii I Psikhiatrii imeni S.S. Korsakova. 105 (2): 46–50. PMID 15792142.
- ^ Peretti CS, 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): 175–181. doi:10.1007/s00213-004-1869-8. PMID 15138753. S2CID 24952829.
- ^ Evidente VG (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.
- ^ Tschopp L, Salazar Z, Gomez Botello MT, Roca CU, Micheli F (2010). "Impulse control disorder and piribedil: report of 5 cases". Clinical Neuropharmacology. 33 (1): 11–13. doi:10.1097/WNF.0b013e3181c4ae2e. PMID 19959959. S2CID 30844295.
- ^ a b TRIVASTAL Retard 50 (piribedil) Prescribing Information, Servier Laboratories, April 2008. [1] Archived 19 December 2012 at the Wayback Machine
- ^ Gouraud A, Millaret A, Descotes J, Vial T (2011). "Piribedil-induced sleep attacks in patients without Parkinson disease: a case series". Clinical Neuropharmacology. 34 (3): 104–107. doi:10.1097/WNF.0b013e31821f0d8b. PMID 21586915. S2CID 22169346.
- ^ Arnsten AF, Murphy B, Merchant K (October 2000). "The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys". Neuropsychopharmacology. 23 (4): 405–10. doi:10.1016/S0893-133X(00)00133-0. PMID 10989267. S2CID 16143246.
- ^ Nagaraja D, Jayashree S (September 2001). "Randomized study of the dopamine receptor agonist piribedil in the treatment of mild cognitive impairment". The American Journal of Psychiatry. 158 (9): 1517–9. doi:10.1176/appi.ajp.158.9.1517. PMID 11532743.
- ^ Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, Millan MJ (November 2002). "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. doi:10.1124/jpet.102.039875. PMID 12388667. S2CID 35238120.
- ^ a b Schubert-Zsilavecz M. "Piribedil". Neue Arzneimittel 2008 (in German).
