Piribedil
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| Clinical data | |
|---|---|
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral |
| ATC code | N04BC08 (WHO) |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | 10% (peak at 1 hour) |
| Protein binding | 70–80% |
| Metabolism | extensive hepatic |
| Biological half-life | 1.7–6.9 hours |
| Excretion | Renal (68%) and biliary (25%) |
| Identifiers | |
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| CAS Number |
3605-01-4  |
| PubChem (CID) | 4850 |
| IUPHAR/BPS | 49 |
| ChemSpider |
4684  |
| UNII |
DO22K1PRDJ |
| KEGG |
D07305 |
| ChEMBL |
CHEMBL1371770 |
| ECHA InfoCard | 100.020.695 |
| Chemical and physical data | |
| Formula | C16H18N4O2 |
| Molar mass | 298.340 g/mol |
| 3D model (Jmol) | Interactive image |
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| (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
- 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 elderly
- 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 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]
Dosage
Parkinson's disease
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
One tablet daily at the end of the main meal. In severe cases: two tablets daily in two doses.
Adverse 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.[8][9]
Interactions
Dopamine antagonists reduce the effect of piribedil.
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.
Receptor affinities
- Dopamine receptor agonist, selective for subtypes D2 and D3.
- Dopamine receptor antagonist, selective for subtypes D4.[10][11]
- Adrenergic receptor antagonist, subtypes α2A and α2C: could be the reason why piribedil seems to cause less drowsiness than other dopamine agonists.[12]
- Lack of affinity to serotonin receptor 5-HT2B: theoretically no risk of heart valve impairment.[12]
See also
- Piribedil structure components:
- Other dopamine agonists:
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- 1 2 TRIVASTAL® Retard 50 (piribedil) Prescribing Information, Servier Laboratories, April 2008.
- ↑ 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.
- ↑ Arnsten et al., 2000; Nagaraja and Jayashree, 2001. "Piribedil".
- ↑ 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" (PDF). J. Pharmacol. Exp. Ther. 303 (2): 812. doi:10.1124/jpet.102.039875. PMID 12388667.
- 1 2 Schubert-Zsilavecz, M. "Piribedil". Neue Arzneimittel 2008 (in German).