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Российский физиологический журнал им. И.М. Сеченова, 2023, T. 109, № 10, стр. 1331-1348

Молекулярные механизмы действия вальпроевой кислоты на сигнальные системы и функционирование мозга

А. Н. Турсунов 1, Д. С. Васильев 2, *, Н. Н. Наливаева 2, **

1 Санкт-Петербургский государственный университет
Санкт-Петербург, Россия

2 Институт эволюционной физиологии и биохимии им. И.М. Сеченова РАН
Санкт-Петербург, Россия

* E-mail: dvasilyev@bk.ru
** E-mail: natalia.nalivaeva@outlook.com

Поступила в редакцию 23.06.2023
После доработки 09.09.2023
Принята к публикации 22.09.2023

Аннотация

Вальпроевая кислота (вальпроат, ВА) уже несколько десятилетий широко используется как противоэпилептическое средство, а также в лечении биполярного аффективного расстройства. На протяжении многих лет способность ВА купировать эпилептические приступы разного характера связывали с усилением ГАМКергической нейротрансмиссии, угнетением глутаматергической нейротрансмиссии и общим снижением гиперактивности ЦНС путем воздействия на ионные каналы, однако точные механизмы реализации противосудорожного эффекта ВА до сих пор не ясны. С течением времени стало известно о влиянии ВА на другие нейромедиаторные системы, ферменты и внутриклеточные сигнальные пути, что, однако, не объясняет эффективность препарата в качестве антиконвульсанта и нормотимика, а лишь расширяет его фармакологический профиль. За последние 10 лет фокус интереса к ВА сместился в связи с его способностью изменять экспрессию генов как путем ингибирования деацетилаз гистонов, так и изменением уровня метилирования ДНК, и новые исследования скорее раскрывают альтернативные механизмы его действия, чем пытаются проверить и подтвердить ранее выдвинутые гипотезы.

Ключевые слова: вальпроевая кислота, эпилепсия, депрессия, расстройства аффективного спектра, регуляция экспрессии генов, ингибитор деацетилаз гистонов, нейропротекция

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