toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0869-7922-2026-34-3-185-198hthaeatoxreview-1111Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯPREVENTIVE TOXICOLOGYМетодические приёмы изучения механизмов действия и интерпретации эффектов агонистов каппа-опиоидных рецепторов (обзор литературы)Methodological approaches for studying the mechanisms of action and interpreting the effects of kappa-opioid receptor agonists (literature review)https://orcid.org/0000-0002-3903-4406СубботинаСветлана НиколаевнаSubbotinaSvetlana N.

Кандидат биологических наук, старший научный сотрудник Федерального Государственного Бюджетного научно-исследовательского испытательного института военной медицины Министерства обороны Российской Федерации, 195043, Санкт-Петербург, Россия

e-mail: ssubbotina@inbox.ru

Candidate of Biol. Sciences, senior researcher of the Federal State Budgetary Scientific Research Testing Institute of the Ministry of Defense of the Russian Federation, St. Petersburg, 195043, Russian Federation

e-mail: ssubbotina@inbox.ru

ssubbotina@inbox.ruhttps://orcid.org/0009-0006-1958-3615ЩербининаКсения ЭдуардовнаShcherbininaKseniya E.

Лаборант-исследователь Федерального Государственного Бюджетного научно-исследовательского испытательного института военной медицины Министерства обороны Российской Федерации, 195043, Санкт-Петербург, Россия

e-mail: gniiivm_4@mil.ru

Laboratory researcher of the Federal State Budgetary Scientific Research Testing Institute of the Ministry of Defense of the Russian Federation, St. Petersburg, 195043, Russian Federation

e-mail: gniiivm_4@mil.ru

gniiivm_4@mil.ruhttps://orcid.org/0000-0002-4592-5352НикифоровАлександр СергеевичNikiforovAlexander S.

Доктор биологических наук, профессор, ведущий научный сотрудник Федерального Государственного Бюджетного научно-исследовательского испытательного института военной медицины Министерства обороны Российской Федерации, 195043, Санкт-Петербург, Россия

e-mail: gniiivm_4@mil.ru

Doctor of Biol. Sciences, professor, leading researcher of the Federal State Budgetary Scientific Research Testing Institute of the Ministry of Defense of the Russian Federation, St. Petersburg, 195043, Russian Federation

e-mail: gniiivm_4@mil.ru

gniiivm_4@mil.ruhttps://orcid.org/0000-0001-5646-0880ЮдинМихаил АнатольевичYudinMikhail A.

Доктор медицинских наук, профессор, начальник научно-исследовательского испытательного центра (медико-биологической защиты) Федерального Государственного Бюджетного научно-исследовательского испытательного института военной медицины Министерства обороны Российской Федерации, 195043, Санкт-Петербург, Россия

e-mail: gniiivm_4@mil.ru

Doctor of Med. Sciences, professor, head of the Scientific Research Testing center (biomedical protection) of the Federal State Budgetary Scientific Research Testing Institute of the Ministry of Defense of the Russian Federation, St. Petersburg, 195043, Russian Federation

e-mail: gniiivm_4@mil.ru

gniiivm_4@mil.ruФГБУ «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны Российской ФедерацииРоссияState Research and Testing Institute of Military Medicine of the Ministry of Defense of the Russian FederationRussian Federation202630062026343185198Copyright © Субботина С.Н., Щербинина К.Э., Никифоров А.С., Юдин М.А., 20262026Субботина С.Н., Щербинина К.Э., Никифоров А.С., Юдин М.А.Subbotina S.N., Shcherbinina K.E., Nikiforov A.S., Yudin M.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.toxreview.ru/jour/article/view/1111

Поиск новых высокоэффективных обезболивающих средств, лишённых побочных эффектов агонистов µ-опиоидных рецепторов (лекарственная зависимость, угнетение дыхания, расстройства желудочно-кишечного тракта), – одно из приоритетных направлений развития современной медицины. Большой интерес в этом плане представляют селективные агонисты к-опиоидных рецепторов, обладающие наравне с агонистами µ-опиоидных рецепторов выраженным обезболивающим эффектом. Однако их широкому внедрению в медицинскую практику препятствует высокий риск развития аффективных расстройств. Кроме того, отсутствие единого методического подхода к оценке побочных эффектов агонистов к-опиоидных рецепторов на этапе доклинического изучения влечёт за собой разрозненность данных и затрудняет формирование надёжной системы прогнозирования их терапевтического потенциала и профиля безопасности.

Материалом для анализа послужили источники литературы, представленные в библиографических базах PubMed, Scopus, Web of Science, MedLine, РИНЦ и eLIBRARY.RU.

В статье обсуждаются результаты отечественных и зарубежных исследований, посвящённых методам оценки и интерпретации эффектов соединений с к‑опиоидной активностью. Показана необходимость применения комплексного подхода, который включает методы молекулярного и клеточного моделирования, исследования на изолированных тканях, доклинические и строго регламентированные клинические испытания. Разработана блок-схема, отражающая структуру экспериментального изучения механизма действия и фармакологических эффектов агонистов к-опиоидных рецепторов.

Систематизация стратегий изучения позволит повысить точность оценки терапевтической активности, переносимости и безопасности соединений данного класса, что, безусловно, будет способствовать повышению прогностической значимости получаемых данных, а также снизит трудоёмкость и продолжительность исследований.

Участие авторов

Участие авторов: Субботина С.Н. – концепция и дизайн статьи, сбор материала и обработка данных, написание и редактирование текста; Щербинина К.Э. – сбор материала и обработка данных, написание и оформление текста статьи; Никифоров А.С. – редактирование, критический пересмотр рукописи; Юдин М.А. – редактирование, утверждение окончательного варианта статьи. Все соавторы – ответственность за целостность всех частей статьи.

Конфликт интересов

Конфликт интересов. Авторы заявляют об отсутствии явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Исследование выполнено без финансовой поддержки.

Поступила в редакцию

Поступила в редакцию: 25 ноября 2025 / Поступила после исправления: 25 февраля 2026 / Принята в печать: 01 июня 2026 / Опубликована: 30 июня 2026

The search for new highly analgesic agents devoid of the side effects characteristic of the µ-opioid receptors agonists (drug dependence, respiratory depression, gastrointestinal disorders) is one of the priorities in the development of modern medicine. In this regard, selective k-opioid receptor agonists are of considerable interest, as they exhibit a pronounced analgesic effect comparable to that of µ-opioid receptor agonists. However, their widespread introduction into medical practice is limited by a high risk of affective disorders. In addition, the lack of a unified methodological approach to the assessing of side effects of k-opioid receptor agonists at the preclinical study stage leads to fragmented data and makes it difficult to form a reliable system for predicting their therapeutic potential and safety profile.

The material for the analysis was the literature sources presented in the bibliographic databases PubMed, Scopus, Web of Science, MedLine, RSCI and eLIBRARY.RU.

The article discusses the results of domestic and foreign studies on methods for evaluating and interpreting the effects of compounds with k-opioid activity. The necessity of applying a comprehensive approach is demonstrated, including molecular and cellular modeling methods, studies on isolated tissues, preclinical investigations, and strictly regulated clinical trials. A flowchart reflecting the structure of the experimental study of the mechanism of action and pharmacological effects of k-opioid receptor agonists has been developed.

The systematization of study strategies will improve the accuracy of assessing the therapeutic activity, tolerability and safety of compounds of this class, which will help to increase the prognostic significance of the data obtained, as well as reduce the complexity and duration of research.

Author contribution

Author contribution: Subbotina S.N. – the concept and design of the study, collection of material and data processing, text writing and editing; Shcherbinina K.E. – collection of material and data processing, text writing and editing; Nikiforov A.S. – editing, critical revision of the manuscript; Yudin M.A. – editing, approval of the final version of the article. All co-authors – responsibility for the integrity of all parts of the article.

Conflict of interest

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding

Funding. The study had no sponsorship.

Received

Received: November 25, 2025 / Revised: February 25, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026

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