medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-2-63-74medsovet-6014Research ArticleНЕЙРОДЕГЕНЕРАТИВНЫЕ ЗАБОЛЕВАНИЯNEURODEGENERATIVE DISEASESПрактические аспекты назначения противопаркинсонических препаратов. Место амантадинов в лечении болезни ПаркинсонаPractical aspects of prescribing antiparkinsonian drugs. The place of amantadines in the management of Parkinson’s diseasehttps://orcid.org/0000-0002-7044-3013ТитоваН. В.TitovaN. V.

Титова Наталия Владимировна, к.м.н., доцент кафедры неврологии, нейрохирургии и медицинской генетики лечебного факультета, Российский национальный исследовательский медицинский университет им. Н.И. Пирогова; научный сотрудник отдела нейродегенеративных заболеваний, Федеральный центр мозга и нейротехнологий

117997, Москва, ул. Островитянова, д. 1117997, Москва, ул. Островитянова, д. 1, стр. 10 

Nataliya V. Titova, Cand. of Sci. (Med.), Associate Professor of the Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University; Researcher of the Department of Neurodegenerative Diseases, Federal Center of Brain and Neurotechnologies

1, Ostrovityanov St., Moscow, 1179971, Bldg. 10, Ostrovityanov St., Moscow, 117997 

nattitova@yandex.ruhttps://orcid.org/0000-0003-4764-3399ПортупеевА. А.PortupeevA. A.

Портупеев Артем Алексеевич, студент

127473, Москва, ул. Делегатская, д. 20, стр. 1

Artem A. Portupeev, Student

20, Bldg. 1, Delegateskaya St., Moscow, 127473

interceple@gmail.comРоссийский национальный исследовательский медицинский университет им. Н.И. Пирогова; Федеральный центр мозга и нейротехнологийРоссияPirogov Russian National Research Medical University; Federal Center of Brain and NeurotechnologiesRussian FederationМосковский государственный медико-стоматологический университет им. А.И. ЕвдокимоваРоссияYevdokimov Moscow State University of Medicine and DentistryRussian Federation202111032021026374Copyright © Титова Н.В., Портупеев А.А., 20212021Титова Н.В., Портупеев А.А.Titova N.V., Portupeev A.A.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/6014

Лечение двигательных симптомов болезни Паркинсона (БП) включает в себя назначение дофаминергических, а также недофаминергических препаратов в моно- или в комбинированной терапии. Одним из ключевых лекарственных средств при БП является леводопа, признанная «золотым стандартом». Леводопа может также использоваться в качестве диагностического теста для верификации диагноза «БП». Другими противопаркинсоническими препаратами являются препараты, работающие через систему дофамина (ингибиторы МАО-В, агонисты дофаминовых рецепторов (АДР), ингибиторы COMT), а также через систему глутамата, в частности, блокаторы NMDA-рецепторов (амантадины). Успешность лечения БП зависит от правильного выбора стартового препарата и корректности последующего лечения. Основными параметрами, которые индивидуализировано определяют препарат для инициации терапии, являются возраст пациента, выраженность и тип двигательного дефицита, состояние когнитивных функций и образ жизни. Несмотря на то что леводопа является самым эффективным препаратом, ее использование неизбежно ведет к развитию моторных флуктуаций и дискинезий. До назначения леводопы, помимо ингибиторов МАО-В и агонистов дофаминовых рецепторов (АДР), в качестве монотерапии могут использоваться амантадины. При замене противопаркинсонического препарата необходимо использовать коэффициент для расчета эквивалентной дозы леводопы. По мере прогрессирования заболевания на развернутой стадии БП применяются подходы для коррекции двигательных осложнений длительной леводопа-терапии. Моторные флуктуации требуют изменения режима дозирования леводопы (суточной дозы и кратности приема), а также добавления дополнительного препарата АДР, ингибитора МАО-В или ингибитора COMT. При развитии дискинезий их коррекция зависит от их типа. Самый частый вид дискинезий – дискинезии пика дозы, появляющиеся на фоне максимальной концентрации леводопы в плазме крови. Добавление к леводопе амантадина обеспечивает быстрый и долговременный антидискинетический эффект, что подтверждено в открытых и двойных слепых плацебо-контролируемых исследованиях. По сравнению с амантадина хлоридом, амантадина сульфат обладает более стабильными фармакокинетическими параметрами и лучшим профилем безопасности. Раствор амантадина сульфата для парентерального введения является препаратом для выведения пациентов из состояния декомпенсации или акинетического криза. Спектр действия амантадинов при БП также включает положительное влияние на утомляемость и апатию. А по данным проведенных исследований применение амантадинов у пациентов с БП может способствовать увеличению продолжительности жизни, положительно влиять на выживаемость и снижать риск деменции.

Treatment of Parkinson’s disease (PD) includes the administration of dopaminergic and occasionally non-dopaminergic drugs, in mono- or in combination therapy. One of the key drug used to treat Parkinson’s disease is levodopa considered a gold standard. In addition levodopa can also be used as a challenge test to confirm the accuracy of diagnosis of PD known as the “Levodopa challenge test”. However many non levodopa class of drugs are also used and consist of dopamine agonists (ADRs), MAO-B and COMT inhibitors, as well as drugs working on glutamate such as a group of drug with NMDA receptor inhibitor activity (amantadines). The successful treatment of PD therefore depends on the correct choice of drugs to initiate treatment and sustainance of such therapy. The main parameters for personolised treatment include the patient’s age, severity and pattern of motor deficit, the state of cognitive function and lifestyle. Levodopa, although the most effective, is almost invariably associated with motor fluctuations and dyskinesias. Before prescribing levodopa, in addition to MAO-B inhibitors and ADRs, amantadines can be used as a monotherapy. Once replacement of therapy is required, then it is necessary to use a coefficient to calculate an equivalent dose of levodopa known as the levodopa equivalent dose. Progression of PD is inevitable inspite of adequate symptomatic therapy and at the advanced stage of PD approaches for the management of motor complications of levodopa need to be considered. For motor fluctuations these strategies require a change in the dosage regimen of levodopa (daily dose and frequency of intake), as well as the addition of an adjunct drug – ADRs, MAO-B inhibitor or COMT inhibitor. When dyskinesias arise, the management depends on correct identification of the type of dyskiensias. The commonest type of dyskinesia is peak dose dyskinesias related to peak plasma levodopa levels after intake. Amantadine provides a quick and long-lasting antidyskinetic effect which has been confirmed in open label as well as double-blind placebo-controlled studies. Compared to аmantadine chloride, amantadine sulfate has more stable pharmacokinetic parameters and a better safety profile. In addition, parenteral administration of amantadine sulfate can be utilized for severely ill patients with akinetic crisis in PD. Amantadine also has a broad spectrum effect and these may include improvement of fatigue and apathy. Some data also suggest that the use of amantadine in patients may increase life expectancy, improve survival and reduce the risk of dementia.

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