mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2022.019mes-187Research ArticleОБЗОРREVIEWМетоды профилактики и терапии судорожного синдрома при отравлении конвульсантами холинергического рядаMethods for prevention and treatment of convulsive disorders associated with сholinergic convulsant intoxicationЗоринаВ. Н.ZorinaV. N.

Вероника Николаевна Зорина

ул. Бехтерева, д. 1, г. Санкт-Петербург, 192019

Veronika N. Zorina

Bekhtereva, 1, Saint-Petersburg, 192019

uchsovet@toxicology.ruЕвдокимоваЕ. А.EvdokimovaE. A.

г. Санкт-Петербург

Saint-Petersburg

РейнюкВ. Л.RejniukV. L.

г. Санкт-Петербург

Saint-Petersburg

Научно-клинический центр токсикологии имени академика С. Н. Голикова Федерального медико-биологического агентстваРоссияGolikov Scientific and Clinical Center of Toxicology of the Federal Medical and Biological AgencyRussian Federation2022281020242421421Copyright © Зорина В.Н., Евдокимова Е.А., Рейнюк В.Л., 20242024Зорина В.Н., Евдокимова Е.А., Рейнюк В.Л.Zorina V.N., Evdokimova E.A., Rejniuk V.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/187

Фосфорорганические соединения (ФОС) и карбаматы — распространенная причина отравлений, ассоциированных с развитием судорожного синдрома. Эти холинергические вещества образуют связь с ацетилхолинэстаразой (АХЭ), что способствует накоплению ацетилхолина в нервных синапсах и приводит к характерным токсическим проявлениям, в том числе к развитию судорог. Стандартная антидотная терапия обеспечивает достаточный контроль симптомов, ослабляет судороги и снижает смертность только при назначении на самой ранней стадии отравления либо при профилактическом введении. Традиционно применяют атропин, который блокирует мускариновые холинергические рецепторы в парасимпатической нервной системе и уменьшает активность сокращения гладких мышц, а также оксимы, реактивирующие обратимо ингибированную АХЭ в никотиновых холинергических синапсах скелетных мышц. Если их недостаточно, для купирования судорог и профилактики развития органических повреждений головного мозга, посттравматической эпилепсии применяют средства бензодиазепинового ряда, взаимодействующие с рецепторами γ- аминомасляной кислоты. Единых официальных руководств на случай, когда антидоты не действуют или действуют недостаточно эффективно, не существует. Нежелательные побочные эффекты и прогрессирующее снижение эффективности существующих средств через 30 мин после воздействия ФОС обуславливают необходимость поиска новых средств. Среди разрабатываемых подходов — комбинированные схемы лечения, новые лекарственные формы, создание оригинальных или модификация существующих молекул, рассмотрению которых посвящен настоящий обзор.

Organophosphates (OPs) and carbamates are a common cause of intoxication associated with convulsive disorders. These cholinergic substances form a bond with acetylcholinesterase (AChE), thus contributing to accumulation of acetylcholine in synapses and causing typical manifestations of toxicity, including seizures. Standard antidote therapy provides sufficient symptom control, reduces seizures and decreases mortality only in case of prescription at the early stage of poisoning or preventive administration. Traditionally, atropine is used, that blocks the activity of the muscarinic cholinergic receptors in the parasympathetic nervous system and reduce the smooth muscle contraction activity, along with oximes that reactivate the reversibly inhibited AChE in the nicotinic acetylcholine receptors found in skeletal muscle. If these are not sufficient, benzodiazepines that interact with γ-aminobutyric acid receptors are used to jugulate seizures, prevent organic brain desease and post-traumatic epilepsy. There are no unified guidelines for the cases of antidotes having no effect or insufficient efficacy of antidotes. Unwanted side effects of the existing drugs and progressive decrease of efficiency within 30 min after exposure to OPs necessitate the search for new agents. Combination therapy, new dosage forms, developing original molecules or modifying the existing ones are among the developed approaches discussed in our review.

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