medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-9-34-38medsovet-2473Research ArticleПАРКИНСОНИЗМPARKINSONISMАмантадин при болезни Паркинсона современные возможности долговременной терапииAmantadine in parkinson’s disease: modern possibilities of long-term therapyПолещукВ. В.PoleshchukV. V.

Москва

Moscow

ИллариошкинС. Н.IllarioshkinS. N.

Москва

Moscow

ФГБНУ Научный центр неврологииРоссияScientific Center of Neurology, Federal State Budgetary Research InstituteRussian Federation201829052018093438Copyright © Полещук В.В., Иллариошкин С.Н., 20182018Полещук В.В., Иллариошкин С.Н.Poleshchuk V.V., Illarioshkin S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/2473

Долговременная терапия болезни Паркинсона (БП) с помощью дофаминергических средств закономерно сопровождается появлением флуктуаций симптомов и дискинезий, причем эти осложнения являются чрезвычайно важным фактором, неблагоприятно влияющим на качество жизни. В патофизиологии лекарственных дискинезий большую роль играет гиперактивность глутаматных NMDA-рецепторов полосатого тела, поэтому в настоящее время общепризнанным способом борьбы с дискинезиями является применение антиглутаматергических средств, и в первую очередь амантадина. В настоящей статье обобщаются современные представления о механизмах действия и клинических эффектах амантадиновых производных у пациентов с различными стадиями БП, с акцентом на антидискинетическом действии данной группы противопаркинсонических средств. Представлены преимущества амантадина сульфата (ПК-Мерц) над другими лекарственными формами (фармакокинетика, длительность эффекта, переносимость, возможность внутривенного инфузионного применения), в том числе при проведении терапии острой декомпенсации БП.

The long-term therapy of Parkinson’s disease (PD) with dopaminergic drugs is naturally accompanied by the fluctuations in symptoms and dyskinesia, and these complications are an extremely important factor that adversely affects the quality of life. The hyperactivity of glutamate NMDA receptors of the striatum plays an important role in the pathophysiology of medicinal dyskinesia, so the use of anti-glutamatergic agents, primarily amantadine, is currently the common method of combating dyskinesia. This article summarizes the current understanding of the mechanisms of action and the clinical effects of amantadine derivatives in patients with different stages of PD, with an emphasis on the antidiskinetic effect of this group of antiparkinsonian agents. It also presents the advantages of amantadine sulphate (PK-Merz) over other dosage forms (pharmacokinetics, duration of effect, tolerability, possibility of intravenous infusion administration), including those in the treatment of acute decompensation of PD.

болезнь Паркинсонатерапиялекарственные дискинезииамантадинПК-МерцParkinson’s diseasetherapydrug dyskinesiaamantadinePK-MerzReferencesParkinson J. An essay on the shaking palsy. London: Sherwood, 1817.Parkinson J. An essay on the shaking palsy. London: Sherwood, 1817.Jenner P, Morris HR, Robbins TW et al. Parkinson’s disease – the debate on the clinical phenomenology, aetiology, pathology and pathogenesis. J Park Dis, 2013, 3: 1–11.Jenner P, Morris HR, Robbins TW et al. Parkinson’s disease – the debate on the clinical phenomenology, aetiology, pathology and pathogenesis. J Park Dis, 2013, 3: 1–11.Poewe W, Seppi K, Tanner CM. Parkinson disease. Nat Rev Dis Primers, 2017, 3: 17013.Poewe W, Seppi K, Tanner CM. Parkinson disease. Nat Rev Dis Primers, 2017, 3: 17013.Литвиненко И.В. Болезнь Паркинсона. М: Миклош, 2006.Litvinenko IV. Parkinson’s disease. M: Miklos, 2006Olanow CW, Schapira AHV. Therapeutic prospects for Parkinson disease. Ann Neurol, 2013, 74: 337–347.Olanow CW, Schapira AHV. Therapeutic prospects for Parkinson disease. Ann Neurol, 2013, 74: 337–347.Левин О.С., Федорова Н.В. Болезнь Паркинсона. М.: МЕДпресс-информ, 2014./Levin OS, Fedorova NV. Parkinson’s disease. М.: MEDpress-inform, 2014.Fahn S, Poewe W. Levodopa: 50 years of a revolutionary drug for Parkinson disease. Mov Disord, 2015, 30: 1–3.Fahn S, Poewe W. Levodopa: 50 years of a revolutionary drug for Parkinson disease. Mov Disord, 2015, 30: 1–3.Hornykiewicz O. L-DOPA. J Parkinson’s Dis, 2017, 7: 3–10.Hornykiewicz O. L-DOPA. J Parkinson’s Dis, 2017, 7: 3–10.Руководство по диагностике и лечению болезни Паркинсона (под ред. С.Н. Иллариошкина, О.С. Левина). М.: МЕДпрессинформ, 2016.Guidance on the diagnosis and treatment of Parkinson’s Disease (edited by Illarioshkina SN, Levin OS). М.: MEDPRESSINFORM, 2016.Jenner P. Pathophysiology and biochemistry of dyskinesia: clues for the development of nondopaminergic treatments. J Neurol, 2000, 247(Suppl.2): II43–II50.Jenner P. Pathophysiology and biochemistry of dyskinesia: clues for the development of nondopaminergic treatments. J Neurol, 2000, 247(Suppl.2): II43–II50.Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol, 2006, 63: 1756–1760.Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol, 2006, 63: 1756–1760.Chase TN, Engber TM, Mouradian MM. Contribution of dopaminergic and glutamatergic mechanisms to the pathogenesis of motor response complications in Parkinson’s disease. Adv Neurol, 1996, 69: 497–501.Chase TN, Engber TM, Mouradian MM. Contribution of dopaminergic and glutamatergic mechanisms to the pathogenesis of motor response complications in Parkinson’s disease. Adv Neurol, 1996, 69: 497–501.Нодель М.Р., Яхно Н.Н. Двигательные флуктуации и дискинезии при болезни Паркинсона: новые возможности терапии. Неврологический журнал, 2007, 2: 26–33.Nodel MR, Yakhno NN. Motor fluctuations and dyskinesia in Parkinson’s disease: new therapeutic options. Nevrologicheskiy Zhurnal, 2007, 2: 26-33.Иллариошкин С.Н., Федотова Е.Ю., Селиверстов Ю.А. Современные высокотехнологичные методы лечения болезни Паркинсона. В кн.: Болезни мозга – медицинские и социальные аспекты (под ред. Е.И. Гусева, А.Б. Гехт). М.: Буки-Веди, 2016: 543–552.Illariyoshkin SN, Fedotova EYu, Seliverstov YuA. Modern high-tech treatments for Parkinson’s disease. In the book: Brain Diseases - Medical and Social Aspects (edited by Gusev EI, Gekht AB). Moscow: Buki-Vedi, 2016: 543-552.Brotchie JM, Lee J, Venderova K. Levodopainduced dyskinesia in Parkinson’s disease. J Neural Transm, 2005, 112: 359–391.Brotchie JM, Lee J, Venderova K. Levodopainduced dyskinesia in Parkinson’s disease. J Neural Transm, 2005, 112: 359–391.Schapira A. Present and future drug treatment for Parkinson’s disease. J Neurol Neurosurg Psychiatry, 2005, 76: 1472–1478.Schapira A. Present and future drug treatment for Parkinson’s disease. J Neurol Neurosurg Psychiatry, 2005, 76: 1472–1478.Иллариошкин С.Н. Производные амантадина в лечении болезни Паркинсона. Нервные болезни, 2016, 3: 14–19.Illariyoshkin SN. Derivatives of amantadine in the treatment of Parkinson’s disease. Nervnye Bolezni, 2016, 3: 14-19Cersósimo MG, Micheli FE. Antiglutamatergic drugs in the treatment of Parkinson’s disease. In: C. Koller, E. Melamed (eds). Handbook of Clinical Neurology, Vol. 84: Parkinson’s disease and related disorders. Part II. Elsevier, 2007: 127–136.Cersósimo MG, Micheli FE. Antiglutamatergic drugs in the treatment of Parkinson’s disease. In: C. Koller, E. Melamed (eds). Handbook of Clinical Neurology, Vol. 84: Parkinson’s disease and related disorders. Part II. Elsevier, 2007: 127–136.Schwab RS, England AC, Poskanzer DC et al. Amantadine in the treatment of Parkinson’s disease. JAMA, 1969, 208: 1168–1170.Schwab RS, England AC, Poskanzer DC et al. Amantadine in the treatment of Parkinson’s disease. JAMA, 1969, 208: 1168–1170.Stoof JC, Booij J, Drukarch B. Amantadine as N-methyl-D-aspartic acid receptor antagonist: new possibilities for therapeutic applications. Clin Neurol Neurosurg, 1992, 94: 4–6.Stoof JC, Booij J, Drukarch B. Amantadine as N-methyl-D-aspartic acid receptor antagonist: new possibilities for therapeutic applications. Clin Neurol Neurosurg, 1992, 94: 4–6.Kornhuber J, Quack G, Danysz W et al. Therapeutic brain concentration of the NMDA receptor antagonist amantadine. Neuropharmacology, 1995, 34: 713–721.Kornhuber J, Quack G, Danysz W et al. Therapeutic brain concentration of the NMDA receptor antagonist amantadine. Neuropharmacology, 1995, 34: 713–721.Butzer JF, Silver DE, Sahs AL. Amantadine in Parkinson’s disease. A double blind, placebo controlled, crossover study with long term follow up. Neurology, 1975, 25: 603–606.Butzer JF, Silver DE, Sahs AL. Amantadine in Parkinson’s disease. A double blind, placebo controlled, crossover study with long term follow up. Neurology, 1975, 25: 603–606.Schwab RS, England AC, Poskanzer DC et al. Amantadine in the treatment of Parkinson’s disease. JAMA, 1969, 208: 1168–1170.Schwab RS, England AC, Poskanzer DC et al. Amantadine in the treatment of Parkinson’s disease. JAMA, 1969, 208: 1168–1170.Fahn S, Isgreen WP. Long term evaluation of amantadine and levodopa combination in parkinsonism by double blind crossover analysis. Neurology, 1975, 25: 695–700.Fahn S, Isgreen WP. Long term evaluation of amantadine and levodopa combination in parkinsonism by double blind crossover analysis. Neurology, 1975, 25: 695–700.Savery F. Amantadine and a fixed combination of levodopa and carbidopa in the treatment of Parkinson’s disease. Dis Nerv Syst, 1977, 38: 605–608.Savery F. Amantadine and a fixed combination of levodopa and carbidopa in the treatment of Parkinson’s disease. Dis Nerv Syst, 1977, 38: 605–608.Jankovic J, Stacy M. Medical management of levodopa-associated motor complications in patients with Parkinson’s disease. CNS Drugs, 2007, 21: 677–692.Jankovic J, Stacy M. Medical management of levodopa-associated motor complications in patients with Parkinson’s disease. CNS Drugs, 2007, 21: 677–692.Elahi B, Phielipp N, Chen R. N-methyl-Daspartate antagonists in levodopa induced dyskinesia: a meta-analysis. Can J Neurol Sci, 2012, 39: 465–472.Elahi B, Phielipp N, Chen R. N-methyl-Daspartate antagonists in levodopa induced dyskinesia: a meta-analysis. Can J Neurol Sci, 2012, 39: 465–472.Oertel WH, Quinn NP. Parkinson’s disease: drug therapy. Baillieres Clin Neurol, 1997, 6: 89–108.Oertel WH, Quinn NP. Parkinson’s disease: drug therapy. Baillieres Clin Neurol, 1997, 6: 89–108.Metman VL, Del Dotto P, van den Munckhof P et al. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology, 1998, 50: 1323–1326.Metman VL, Del Dotto P, van den Munckhof P et al. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology, 1998, 50: 1323–1326.Blanchet PJ, Konitsiotis S, Chase TN. Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. Mov Disord, 1998, 13: 798–802.Blanchet PJ, Konitsiotis S, Chase TN. Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. Mov Disord, 1998, 13: 798–802.Da Silva-Junior FP, Braga-Neto P, Sueli Monte F, De Bruin VM. Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study. Parkinsonism Relat Disord, 2005, 11: 449–452.Da Silva-Junior FP, Braga-Neto P, Sueli Monte F, De Bruin VM. Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study. Parkinsonism Relat Disord, 2005, 11: 449–452.Luginger E, Wenning GK, Boesch S, Poewe W. Beneficial effects of amantadine on L-dopainduced dyskinesias in Parkinson’s disease. Mov Disord, 2000, 15: 873–878.Luginger E, Wenning GK, Boesch S, Poewe W. Beneficial effects of amantadine on L-dopainduced dyskinesias in Parkinson’s disease. Mov Disord, 2000, 15: 873–878.Rajput AH, Rajput A, Lang AE et al. New use for an old drug: amantadine benefits levodopa induced dyskiensias. Mov Disord, 1998, 13: 851–854.Rajput AH, Rajput A, Lang AE et al. New use for an old drug: amantadine benefits levodopa induced dyskiensias. Mov Disord, 1998, 13: 851–854.Ruicka E, Streiova H, Jech R et al. Amantadine infusion treatment of motor fluctuations and dyskinesias in Parkinson’s disease. J Neural Transm, 2000, 102: 1297–1306.Ruicka E, Streiova H, Jech R et al. Amantadine infusion treatment of motor fluctuations and dyskinesias in Parkinson’s disease. J Neural Transm, 2000, 102: 1297–1306.Del Dotto P, Pavese N, Gambaccini G et al. Intravenous amantadine improves levadopainduced dyskinesias: an acute double-blind placebo-controlled study Mov Disord, 2001, 16: 515–520.Del Dotto P, Pavese N, Gambaccini G et al. Intravenous amantadine improves levadopainduced dyskinesias: an acute double-blind placebo-controlled study Mov Disord, 2001, 16: 515–520.Metman VL, Del Dotto P, Lepoole K et al. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol, 1999, 56: 1383–1386.Metman VL, Del Dotto P, Lepoole K et al. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol, 1999, 56: 1383–1386.Thomas A, Iacono D, Luciano AL et al. Duration of amantadine benefit on dyskinesia of severe Parkinson’s disease. J Neurol Neurosurg Psychiatry, 2004, 75: 141–143.Thomas A, Iacono D, Luciano AL et al. Duration of amantadine benefit on dyskinesia of severe Parkinson’s disease. J Neurol Neurosurg Psychiatry, 2004, 75: 141–143.Wolf E, Seppi K, Katzenschlager R et al. Longterm antidyskinetic efficacy of amantadine in Parkinson’s disease. Mov Disord, 2010, 25: 1357–1363.Wolf E, Seppi K, Katzenschlager R et al. Longterm antidyskinetic efficacy of amantadine in Parkinson’s disease. Mov Disord, 2010, 25: 1357–1363.Грачев И.С., Федорова Н.В. Лекарственные дискинезии при болезни Паркинсона: классификация, влияние на качество жизни и подходы к лечению. В сб.: Болезнь Паркинсона и расстройства движений. Руководство для врачей по материалам I Национального конгресса (под ред. С.Н. Иллариошкина, Н.Н. Яхно). М.: 2008: 88–92.Grachev IS, Fedorova NV. Medicinal dyskinesia in Parkinson’s disease: classification, impact on quality of life and approaches to treatment. In the collection of works: Parkinson’s disease and movement disorders. A guide for practitioner on the materials of the First National Congress (edited by Illarionkina SN, Yakhno NN). M.: 2008: 88-92.Ilzenberg R, Bonuccelli U, Schechtman E et al. Association between amantadine and the onset of dementia in Parkinson’s disease. Mov Disord, 2006, 21: 1375–1379.Ilzenberg R, Bonuccelli U, Schechtman E et al. Association between amantadine and the onset of dementia in Parkinson’s disease. Mov Disord, 2006, 21: 1375–1379.Uitti RJ, Rajput AH, Ahlskog JE et al. Amantadine treatment as an independent predictor of improved survival in Parkinson’s disease. Neurology, 1996, 46: 1551–1552.Uitti RJ, Rajput AH, Ahlskog JE et al. Amantadine treatment as an independent predictor of improved survival in Parkinson’s disease. Neurology, 1996, 46: 1551–1552.Mizuno Y, Takubo H, Mizuta E, Kuno S. Malignant syndrome in Parkinson’s disease: concept and review of the literature. Parkinsonism Relat Disord, 2003, 9: 3–9.Mizuno Y, Takubo H, Mizuta E, Kuno S. Malignant syndrome in Parkinson’s disease: concept and review of the literature. Parkinsonism Relat Disord, 2003, 9: 3–9.Onofri M, Thomas A. Acute akinesia in Parkinson’s disease. Neurology, 2005, 64: 11621169.Onofri M, Thomas A. Acute akinesia in Parkinson’s disease. Neurology, 2005, 64: 11621169.Левин О.С. Феноменология и лечения декомпенсации болезни Паркинсона. Неврол. журнал, 2007, 1: 8–15.Levin OS. Phenomenology and treatment of decompensation of Parkinson’s disease. Nevrol. Zhurnal, 2007, 1: 8-15.Федорова Н.В., Ветохина Т.Н. Нейролептические экстрапирамидные расстройства. В сб.: Болезнь Паркинсона и расстройства движений. Руководство для врачей по материалам II Национального конгресса (под ред. С.Н. Иллариошкина, О.С. Левина). М., 2011: 275–280.Fedorova NV, Vetokhina TN. Neuroleptic extrapyramidal disorders. In the collection of works: Parkinson’s disease and movement disorders. A guide for practitioners on the materials of the II National Congress (edited by Illarioshkina SN, Levin OS). M., 2011: 275-280.Pappa S, Tsouli S, Apostolou G et al. Effects of amantadine on tardive dyskinesia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol, 2010, 33: 271–275.Pappa S, Tsouli S, Apostolou G et al. Effects of amantadine on tardive dyskinesia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol, 2010, 33: 271–275.

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