nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2022-4-103-107nnp-1869Research ArticleREVIEWSОБЗОРЫPiribedil in the treatment of mental and cognitive impairments in Parkinson's diseaseПирибедил в лечении психических и когнитивных нарушений при болезни Паркинсонаhttps://orcid.org/0000-0002-7514-5736ЯковенкоЕ. В.YakovenkoE. V.

Елена Владимировна Яковенко125367, Москва, Волоколамское шоссе, 80

Elena Vladimirovna Yakovenko125367, Moscow, Volokolamskoye Sh., 80

helenaabracham@gmail.comhttps://orcid.org/0000-0002-0555-0445АббасовФ. А.AbbasovF. A.

123098, Москва, ул. Маршала Новикова, 23

123098, Moscow, Marshal Novikov St., 23

ФГБНУ «Научный центр неврологии»РоссияResearch Center of NeurologyRussian FederationФедеральный неврологический центр экстрапирамидных заболеваний и психического здоровья ФГБУ «Государственный научный центр Российской Федерации – Федеральный медицинский биофизический центр им. А.И. Бурназяна» ФМБА РоссииРоссияFederal Neurological Center for Extrapyramidal Diseases and Mental Health, State Scientific Center of the Russian Federation – A.I. Burnazyan Federal Medical Biophysical Center, Russian Federal Medical Biological AgencyRussian Federation202224082022144103107Copyright © Yakovenko E.V., Abbasov F.A., 20222022Яковенко Е.В., Аббасов Ф.А.Yakovenko E.V., Abbasov F.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/1869

Mental and cognitive impairments are common non-motor symptoms of Parkinson's disease (PD), which affect more than half of patients at various stages of the disease. These symptoms significantly reduce the quality of life of patients and their relatives. The article reflects the features of the pathogenesis of mental and cognitive impairments in PD, as well as the role of the dopamine receptor agonist piribedil in their correction. Piribedil, having a good safety and tolerability profile, and also, presumably, having a positive effect on such non-motor symptoms of PD as increased daytime sleepiness, depression, apathy, anhedonia and cognitive functions, can significantly improve the quality of life of patients and their adherence to therapy.

Психические и когнитивные нарушения являются распространенными немоторными симптомами болезни Паркинсона (БП), с которым сталкиваются более половины пациентов на различных стадиях заболевания. Данные симптомы значительно снижают качество жизни пациентов и их родственников. В статье отражены особенности патогенеза психических и когнитивных нарушений при БП, а также роль агониста дофаминовых рецепторов пирибедила в их коррекции. Пирибедил, обладая хорошим профилем безопасности и переносимости, а также, предположительно, оказывая положительный эффект в отношении таких немоторных симптомов БП, как повышенная дневная сонливость, депрессия, апатия, ангедония и когнитивные функции, может значительно повышать качество жизни пациентов и их приверженность терапии.

болезнь Паркинсонанемоторные симптомыапатиядепрессиядеменцияпирибедилParkinson's diseasenon-motor symptomsapathydepressiondementiapiribedilСтатья спонсируется компанией «Сервье».This article has been supported by Servier.ReferencesAlves G, Forsaa EB, Pedersen KF, et al. Epidemiology of Parkinson's disease. J Neurol. 2008 Sep;255 Suppl 5:18-32. doi:10.1007/s00415-008-5004-3Alves G, Forsaa EB, Pedersen KF, et al. Epidemiology of Parkinson's disease. J Neurol. 2008 Sep;255 Suppl 5:18-32. doi:10.1007/s00415-008-5004-3Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct;30(12):1591-601. doi:10.1002/mds.26424Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct;30(12):1591-601. doi:10.1002/mds.26424Todorova A, Jenner P, Ray Chaudhuri K. Non-motor Parkinson's: integral to motor Parkinson's, yet often neglected. Pract Neurol. 2014 Oct;14(5):310-22. doi:10.1136/practneurol-2013-000741. Epub 2014 Apr 3.Todorova A, Jenner P, Ray Chaudhuri K. Non-motor Parkinson's: integral to motor Parkinson's, yet often neglected. Pract Neurol. 2014 Oct;14(5):310-22. doi:10.1136/practneurol-2013-000741. Epub 2014 Apr 3.Fox SH, Katzenschlager R, Lim SY, et al. Update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018 Aug;33(8):1248-66. doi:10.1002/mds.27372. Epub 2018 Mar 23.Fox SH, Katzenschlager R, Lim SY, et al. Update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018 Aug;33(8):1248-66. doi:10.1002/mds.27372. Epub 2018 Mar 23.Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson's disease – an evidencebased medicine review. Mov Disord. 2019 Feb;34(2):180-98. doi:10.1002/mds.27602. Epub 2019 Jan 17.Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson's disease – an evidencebased medicine review. Mov Disord. 2019 Feb;34(2):180-98. doi:10.1002/mds.27602. Epub 2019 Jan 17.Титова НВ, Чаудхури КР. Немоторные симптомы болезни Паркинсона: подводная часть айсберга. Анналы клинической и экспериментальной неврологии. 2017;11(4):5-18. doi:10.18454/ACEN.2017.4.1Titova NV, Chaudhuri КR. Non-motor symptoms of Parkinson’s disease: the submerged part of the iceberg. Annaly klinicheskoy i eksperimental’noy nevrologii = Annals of Clinical and Experimental Neurology. 2017;11(4):5-18. doi:10.18454/ACEN.2017.4.1 (In Russ.)Schrag A, Ben-Shlomo Y, Quinn N. How common are complications of Parkinson’s disease? J Neurol. 2002 Apr;249(4):419-23. doi:10.1007/s004150200032Schrag A, Ben-Shlomo Y, Quinn N. How common are complications of Parkinson’s disease? J Neurol. 2002 Apr;249(4):419-23. doi:10.1007/s004150200032Pagonabarraga J, Kulisevsky J, Strafella AP, et al. Apathy in Parkinson’s disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurol. 2015 May;14(5):518-31. doi:10.1016/S1474-4422(15)00019-8. Epub 2015 Apr 12.Pagonabarraga J, Kulisevsky J, Strafella AP, et al. Apathy in Parkinson’s disease: clinical features, neural substrates, diagnosis, and treatment. Lancet Neurol. 2015 May;14(5):518-31. doi:10.1016/S1474-4422(15)00019-8. Epub 2015 Apr 12.Santangelo G, Trojano L, Barone P, et al. Apathy in Parkinson's disease: diagnosis, neuropsychological correlates, pathophysiology and treatment. Behav Neurol. 2013 Jan 1;27(4):501-13. doi:10.3233/BEN-129025Santangelo G, Trojano L, Barone P, et al. Apathy in Parkinson's disease: diagnosis, neuropsychological correlates, pathophysiology and treatment. Behav Neurol. 2013 Jan 1;27(4):501-13. doi:10.3233/BEN-129025Santangelo G, D’Iorio A, Maggi G, et al. Cognitive correlates of “pure apathy” in Parkinson's disease. Parkinsonism Relat Disord. 2018 Aug;53:101-4. doi:10.1016/j.parkreldis.2018.04.023. Epub 2018 Apr 24.Santangelo G, D’Iorio A, Maggi G, et al. Cognitive correlates of “pure apathy” in Parkinson's disease. Parkinsonism Relat Disord. 2018 Aug;53:101-4. doi:10.1016/j.parkreldis.2018.04.023. Epub 2018 Apr 24.Mentenopoulos G, Katsarou Z, Bostantjopoulou S, et al. Piribedil therapy in Parkinson’s disease. Use of the drug in the retard form. Clin Neuropharmacol. 1989 Feb;12(1):23-8.Mentenopoulos G, Katsarou Z, Bostantjopoulou S, et al. Piribedil therapy in Parkinson’s disease. Use of the drug in the retard form. Clin Neuropharmacol. 1989 Feb;12(1):23-8.Castro-Caldas A, Delwaide P, Jost W, et al. The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson’s disease. Mov Disord. 2006 Apr;21(4):500-9. doi:10.1002/mds.20750Castro-Caldas A, Delwaide P, Jost W, et al. The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson’s disease. Mov Disord. 2006 Apr;21(4):500-9. doi:10.1002/mds.20750Rondot P, Ziegler M. Activity and acceptability of piribedil in Parkinson’s disease: a multicentre study. J Neurol. 1992;239 Suppl 1:S28-34. doi:10.1007/BF00819564Rondot P, Ziegler M. Activity and acceptability of piribedil in Parkinson’s disease: a multicentre study. J Neurol. 1992;239 Suppl 1:S28-34. doi:10.1007/BF00819564Broen MP, Narayen NE, Kuijf ML, et al. Prevalence of anxiety in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2016 Aug;31(8):1125-33. doi:10.1002/mds.26643. Epub 2016 Apr 29.Broen MP, Narayen NE, Kuijf ML, et al. Prevalence of anxiety in Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2016 Aug;31(8):1125-33. doi:10.1002/mds.26643. Epub 2016 Apr 29.Zhu K, van Hilten JJ, Marinus J. Onset and evolution of anxiety in Parkinson's disease. Eur J Neurol. 2017 Feb;24(2):404-11. doi:10.1111/ene.13217. Epub 2016 Dec 29.Zhu K, van Hilten JJ, Marinus J. Onset and evolution of anxiety in Parkinson's disease. Eur J Neurol. 2017 Feb;24(2):404-11. doi:10.1111/ene.13217. Epub 2016 Dec 29.Pertovaara A, Haapalinna A, Sirvio J, et al. Pharmacological properties, central nervous system effects, and potential therapeutic applications of atipamezole, a selective alpha2-adrenoceptor antagonist. CNS Drug Rev. 2005 Autumn;11(3):273-88. doi:10.1111/j.1527-3458.2005.tb00047.xPertovaara A, Haapalinna A, Sirvio J, et al. Pharmacological properties, central nervous system effects, and potential therapeutic applications of atipamezole, a selective alpha2-adrenoceptor antagonist. CNS Drug Rev. 2005 Autumn;11(3):273-88. doi:10.1111/j.1527-3458.2005.tb00047.xTellez S, Colpaert F, Marien M. Acetylcholine release in the rat prefrontal cortex in vivo: modulation by alpha 2-adrenoceptor agonists and antagonists. J Neurochem. 1997 Feb;68(2):778-85. doi:10.1046/j.1471-4159.1997.68020778.xTellez S, Colpaert F, Marien M. Acetylcholine release in the rat prefrontal cortex in vivo: modulation by alpha 2-adrenoceptor agonists and antagonists. J Neurochem. 1997 Feb;68(2):778-85. doi:10.1046/j.1471-4159.1997.68020778.xScheinin M, Sallinen J, Haapalinna A. Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target studies in transgenic mouse models. Life Sci. 2001 Apr 6;68(19-20):2277-85. doi:10.1016/s0024-3205(01)01016-5Scheinin M, Sallinen J, Haapalinna A. Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target studies in transgenic mouse models. Life Sci. 2001 Apr 6;68(19-20):2277-85. doi:10.1016/s0024-3205(01)01016-5Rizk P, Salazar J, Raisman-Vozari R, et al. The alpha2-adrenoceptor antagonist dexefaroxan enhances hippocampal neurogenesis by increasing the survival and differentiation of new granule cells. Neuropsychopharmacology. 2006 Jun;31(6):1146-57. doi:10.1038/sj.npp.1300954Rizk P, Salazar J, Raisman-Vozari R, et al. The alpha2-adrenoceptor antagonist dexefaroxan enhances hippocampal neurogenesis by increasing the survival and differentiation of new granule cells. Neuropsychopharmacology. 2006 Jun;31(6):1146-57. doi:10.1038/sj.npp.1300954Smith L, De Salvia M, Jenner P, et al. An appraisal of the antiparkinsonian activity of piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. Mov Disord. 1996 Mar;11(2):125-35. doi:10.1002/mds.870110203Smith L, De Salvia M, Jenner P, et al. An appraisal of the antiparkinsonian activity of piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. Mov Disord. 1996 Mar;11(2):125-35. doi:10.1002/mds.870110203Smith LA, Jackson MG, Bonhomme C, et al. Transdermal administration of piribedil reverses MPTP-induced motor deficits in the common marmoset. Clin Neuropharmacol. 2000 May-Jun;23(3):133-42. doi:10.1097/00002826-200005000-00002Smith LA, Jackson MG, Bonhomme C, et al. Transdermal administration of piribedil reverses MPTP-induced motor deficits in the common marmoset. Clin Neuropharmacol. 2000 May-Jun;23(3):133-42. doi:10.1097/00002826-200005000-00002Smith LA, Tel BC, Jackson MJ, et al. Repeated administration of piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: a behavioural and biochemical investigation. Mov Disord. 2002 Sep;17(5):887-901. doi:10.1002/mds.10200Smith LA, Tel BC, Jackson MJ, et al. Repeated administration of piribedil induces less dyskinesia than L-dopa in MPTP-treated common marmosets: a behavioural and biochemical investigation. Mov Disord. 2002 Sep;17(5):887-901. doi:10.1002/mds.10200Millan MJ, Cussac D, Milligan G, et al. Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization. J Pharmacol Exp Ther. 2001 Jun;297(3):876-87.Millan MJ, Cussac D, Milligan G, et al. Antiparkinsonian agent piribedil displays antagonist properties at native, rat, and cloned, human alpha(2)-adrenoceptors: cellular and functional characterization. J Pharmacol Exp Ther. 2001 Jun;297(3):876-87.Turle-Lorenzo N, Maurin B, Puma C, et al. The dopamine agonist piribedil with L-DOPA improves attentional dysfunction: relevance for Parkinson’s disease. J Pharmacol Exp Ther. 2006 Nov;319(2):914-23. doi:10.1124/jpet.106.109207. Epub 2006 Aug 18.Turle-Lorenzo N, Maurin B, Puma C, et al. The dopamine agonist piribedil with L-DOPA improves attentional dysfunction: relevance for Parkinson’s disease. J Pharmacol Exp Ther. 2006 Nov;319(2):914-23. doi:10.1124/jpet.106.109207. Epub 2006 Aug 18.Flynn DD, Mash DC. Characterization of L-[3H]nicotine binding in human cerebral cortex: comparison between Alzheimer’s disease and the normal. J Neurochem. 1986;47:1948-54.Flynn DD, Mash DC. Characterization of L-[3H]nicotine binding in human cerebral cortex: comparison between Alzheimer’s disease and the normal. J Neurochem. 1986;47:1948-54.Marighetto A, Valerio S, Philippin JN, et al. Comparative effects of the dopaminergic agonists piribedil and bromocriptine in three different memory paradigms in rodents. J Psychopharmacol. 2008 Jul;22(5):511-21. doi:10.1177/0269881107083836. Epub 2008 Feb 28.Marighetto A, Valerio S, Philippin JN, et al. Comparative effects of the dopaminergic agonists piribedil and bromocriptine in three different memory paradigms in rodents. J Psychopharmacol. 2008 Jul;22(5):511-21. doi:10.1177/0269881107083836. Epub 2008 Feb 28.Brocco M, Dekeyne A, Papp M, et al. Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors. Behav Pharmacol. 2006 Nov;17(7):559-72. doi:10.1097/01.fbp.0000236267.41806.5bBrocco M, Dekeyne A, Papp M, et al. Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors. Behav Pharmacol. 2006 Nov;17(7):559-72. doi:10.1097/01.fbp.0000236267.41806.5bThobois S, Lhommee E, Klinger H, et al. Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil. Brain. 2013 May;136(Pt 5):1568-77. doi:10.1093/brain/awt067. Epub 2013 Mar 29.Thobois S, Lhommee E, Klinger H, et al. Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil. Brain. 2013 May;136(Pt 5):1568-77. doi:10.1093/brain/awt067. Epub 2013 Mar 29.Eggert K, Ohlwein C, Kassubek J, et al. Influence of the nonergot dopamine agonist piribedil on vigilance in patients With Parkinson Disease and excessive daytime sleepiness (PiViCog-PD): an 11-week randomized comparison trial against pramipexole and ropinirole. Clin Neuropharmacol. 2014 JulAug;37(4):116-22. doi:10.1097/WNF.0000000000000041Eggert K, Ohlwein C, Kassubek J, et al. Influence of the nonergot dopamine agonist piribedil on vigilance in patients With Parkinson Disease and excessive daytime sleepiness (PiViCog-PD): an 11-week randomized comparison trial against pramipexole and ropinirole. Clin Neuropharmacol. 2014 JulAug;37(4):116-22. doi:10.1097/WNF.0000000000000041Peretti CS, Gierski F, Harrois S. Cognitive skill learning in healthy older adults after 2 months of double-blind treatment with piribedil. Psychopharmacology. 2004 Nov;176(2):175-81. doi:10.1007/s00213-004-1869-8. Epub 2004 May 12.Peretti CS, Gierski F, Harrois S. Cognitive skill learning in healthy older adults after 2 months of double-blind treatment with piribedil. Psychopharmacology. 2004 Nov;176(2):175-81. doi:10.1007/s00213-004-1869-8. Epub 2004 May 12.Schuck S, Bentue-Ferrer D, Kleinermans D, et al. Psychomotor and cognitive effects of piribedil, a dopamine agonist, in young healthy volunteers. Fundam Clin Pharmacol. 2002 Feb;16(1):57-65. doi:10.1046/j.1472-8206.2002.00070.xSchuck S, Bentue-Ferrer D, Kleinermans D, et al. Psychomotor and cognitive effects of piribedil, a dopamine agonist, in young healthy volunteers. Fundam Clin Pharmacol. 2002 Feb;16(1):57-65. doi:10.1046/j.1472-8206.2002.00070.xStraka I, Minar M, Skorvanek M, et al. Adherence to Pharmacotherapy in Patients With Parkinson's Disease Taking Three and More Daily Doses of Medication. Front Neurol. 2019 Jul 31;10:799. doi:10.3389/fneur.2019.00799. eCollection 2019.Straka I, Minar M, Skorvanek M, et al. Adherence to Pharmacotherapy in Patients With Parkinson's Disease Taking Three and More Daily Doses of Medication. Front Neurol. 2019 Jul 31;10:799. doi:10.3389/fneur.2019.00799. eCollection 2019.Daley DJ, Myint PK, Gray RJ, Deane KH. Systematic review on factors associated with medication non-adherence in Parkinson's disease. Parkinsonism Relat Disord. 2012 Dec;18(10):1053-61. doi:10.1016/j.parkreldis.2012.09.004. Epub 2012 Sep 28.Daley DJ, Myint PK, Gray RJ, Deane KH. Systematic review on factors associated with medication non-adherence in Parkinson's disease. Parkinsonism Relat Disord. 2012 Dec;18(10):1053-61. doi:10.1016/j.parkreldis.2012.09.004. Epub 2012 Sep 28.

The authors declare that there are no conflicts of interest present.