Анальгетическая активность производного имидазо[1,2-а]индола и вовлеченность в нее TRPV1 и κ-опиоидных рецепторов

Авторы

DOI:

https://doi.org/10.18413/rrpharmacology.11.641

Аннотация

Введение. Для ослабления боли применяют различные анальгетики – преимущественно нестероидные противовоспалительные (НПВП) и опиоидные препараты. Учитывая то, что опиоиды могут вызывать угнетение дыхания, психическую и физическую зависимость, привыкание, а НПВП – гастро- и энтеропатии, нефротоксичность, бронхоспазм, кровотечение, нарушение функций сердечно-сосудистой системы, поиск новых молекул, оказывающих анальгезирующее действие через другие клеточные мишени, является актуальным. Цель работы – оценить анальгетическую активность нового производного имидазо[1,2-а]индола на различных моделях боли и его влияние на TRPV1 и κ-опиоидные рецепторы.

Материалы и методы. Определение средней летальной дозы – ЛД50 производного имидазо[1,2-а]индола(лабораторный шифр SV-1010) проводили в опытах на мышах и крысах. Исследование анальгезирующего действия SV-1010 осуществляли с использованием тестов «горячая пластина» (на мышах), «отдергивания хвоста» (на крысах), «давления на лапу» (на крысах), «уксусные корчи» (на мышах), «формалиновый» (на крысах) и на нейропатическую боль (на крысах). Кроме этого, исследовали влияние SV-1010 на ионные каналы TRPV1 (на линии клеток яичников китайского хомячка с индуцированной экспрессией TRPV1-канала крысы) и проверяли вероятность активации κ-опиоидных рецепторов (молекулярным докингом). SV-1010 и референс-препараты диклофенак, индометацин, кеторолак и прегабалин применяли внутрижелудочно.

Результаты исследований и их обсуждение. SV-1010 менее токсично, чем диклофенак, индометацин и кеторолак, оказывает выраженное анальгезирующее действие, при этом по активности и широте терапевтического действия превосходит диклофенак, индометацин, кеторолак и прегабалин.

Точками приложения анальгезирующего действия SV-1010 являются супраспинальный, супраспинальный + периферический, спинальный и периферический уровни организации болевой чувствительности; высокая избирательность блокирования TRPV1 и активирования κ-опиоидных рецепторов.

Заключение. Значительно меньшая острая токсичность (по сравнению с диклофенаком, индометацином и кеторолаком), высокая анальгезирующая активность и большая широта терапевтического действия (по сравнению с диклофенаком, индометацином, кеторолаком и прегабалином) позволяют рекомендовать SV-1010 для дальнейшего доклинического изучения.

Графическая аннотация

Ключевые слова:

анальгетическое действие, производное имидазо[1,2-а]индола, ионные каналы TRPV1, κ-опиоидные рецепторы

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Вклад авторов

Павел А. Галенко-Ярошевский , Кубанский государственный медицинский университет

Corresponding Member of the Russian Academy of Sciences, Doctor Habil. of Medical Sciences, Professor, Head of the Pharmacology Department, Kuban State Medical University, Krasnodar, Russia; e-mail: Galenko.Yaroсhevsky@gmail.com; ORCID ID: https://orсid.org/0000-0003-3190-1437. Author contributions: developing the concept; forming the idea and focus of the study; developing and designing the methodology, and formulating key goals and objectives.

Анаит В. Зеленская, Кубанский государственный медицинский университет

PhD in Medicine, Associate Professor, Pharmacology Department, Kuban State Medical University, Krasnodar, Russia; e-mail: anait_06@mail.ru; ORCID ID: https://orcid.org/0000-0001-9512-2526. Author contributions: analyzing and interpreting the study results; preparing and editing the article, and participating in scientific design.

Константин Ф. Суздалев, Южный федеральный университет

PhD in Chemistry, Associate Professor, Department of Chemistry of Natural and Macromolecular Compounds, Southern Federal University, Rostov-on-Don, Russia; e-mail: kosuzd@mail.ru; ORCID ID: https://orcid.org/0000-0003-4879-0577. Author contributions: synthesis of compound SV-1010, critical revision of the manuscript and provision of valuable comments.

Елена Н. Чуян, Крымский федеральный университет имени В.И. Вернадского

Doctor Habil. of Biological Sciences, Professor, Head of the Department of Human and Animal Physiology and Biophysics, Institute of Biochemical Technologies, Ecology, and Pharmacy, V.I. Vernadsky Crimean Federal University, Simferopol, Russia; e-mail: elena-chuyan@rambler.ru; ORCID ID: https://orcid.org/0000-0001-6240-2732. Author contributions: developing the concept, key goals and objectives; interpreting data; drafting and critically revising the manuscript; participating in scientific design; being responsible for all aspects of the work, the integrity of all parts of the article, and its final version.

Мария Ю. Раваева, Крымский федеральный университет имени В.И. Вернадского

PhD in Biology, Associate Professor, Department of Human and Animal Physiology and Biophysics, Institute of Biochemical Technologies, Ecology and Pharmacy, V.I. Vernadsky Crimean Federal University, Simferopol, Russia; e-mail: ravaevam@yandex.ru; ORCID ID: https://orcid.org/0000-0002-6081-1628. Author contributions: developing the concept, key goals and objectives; interpreting data; critically revising the manuscript; being responsible for all aspects of the work, the integrity of all parts of the article, and its final version.

Роман А. Мурашко, Кубанский государственный медицинский университет

Doctor Habil. of Medical Sciences, Associate Professor, Head of the Department of Public Health and Healthcare No. 1, Kuban State Medical University, Krasnodar, Russia; e-mail: ramurashko@rambler.ru; ORCID ID: https://orcid.org/0000-0001-8873-8461. Author contributions: developing key goals and objectives; critically revising the manuscript, and providing valuable comments.

Павел М. Вассильев

Sci. Biol., Ph.D., Senior Researcher Head of Laboratory for Information Technology in Pharmacology and Computer Modeling of Drugs for Research Center of Innovative Medicines Professor of Chair for Pharmacology and Bioinformatics, Volgograd State Medical University, Volgograd. Russia; e-mail: pvassiliev@mail.ru, ORCID ID: https://orcid.org/0000-0002-8188-5052. Author's contribution: development of key goals and objectives, participation in research on the effect of SV-1010 on k-opioid receptors.

Тереза Р. Глечян , Кубанский государственный медицинский университет

Teaching fellow, Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: t_g91@mail.ru; ORCID ID: https://orcid.org/0009-0002-4983-2433. Author contributions: conducting the study; analyzing and interpreting the data; and participating in the scientific design.

Алина В. Сергеева, Кубанский государственный медицинский университет

Teaching fellow, Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: alina_sergeeva_v@mail.ru; ORCID ID: https://orcid.org/0000-0003-4335-2156. Author contributions: conducting the research; analyzing and interpreting the obtained data; and participating in scientific design.

Елена В. Лейченко , Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук

PhD in Chemistry, Associate Professor, Head of the Laboratory of Molecular Pharmacology and Biomedicine, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia; e-mail: leychenko@gmail.com; ORCID ID: https://orcid.org/0000-0002-2360-1365. Author contributions: developing the key goals and objectives; critically revising the manuscript, and providing valuable comments.

Владислав И. Чубинский-Надеждин , Институт цитологии Российской академии наук

PhD in Biology, Lead Researcher, Laboratory of Ionic Mechanisms of Cell Signaling, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia; e-mail: vchubinskiy@incras.ru; ORCID ID: https://orcid.org/0000-0002-8488-6130. Author contributions: developing the key goals and objectives; critically revising the manuscript, and providing valuable comments.

Ольга Н. Гулевская, Кубанский государственный университет физической культуры, спорта и туризма

PhD in Medicine, Associate Professor, Department of Adaptive Physical Culture, Kuban State University of Physical Education, Sports and Tourism, Krasnodar, Russia; e-mail: olga.stoyalova@bk.ru; ORCID ID:  https://orcid.org/0000-0001-7205-2473. Author contributions: conducting the study; analyzing and interpreting the obtained data, and participating in the scientific design.

Юлия В. Королькова, Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук

PhD in Chemistry, Senior Researcher at the Laboratory of Neuroreceptors and Neuroregulators, M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia; e-mail: yuly@ibch.ru; ORCID ID: https://orcid.org/0000-0001-8556-5366. Author contributions: conducting the research; analyzing and interpreting the data, and participating in the scientific design.

Маргарита М. Шаматова , Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук

PhD student, M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia; e-mail: shamatova.m.m@gmail.com; ORCID ID: https://orcid.org/0009-0007-1511-1538. Author contributions: conducting the research; analyzing and interpreting the data, and participating in the scientific design.

Валерия Ю. Васильева , Институт цитологии Российской академии наук

PhD in Biology, Research fellow, Laboratory of Ionic Mechanisms of Cell Signaling, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia; email: vvasileva@incras.ru; ORCID ID: https://orcid.org/0000-0002-5992-8693. Author contributions: conducting the study; analyzing and interpreting the obtained data, and participating in the scientific design.

Нарек Н. Ишханьян, Кубанский государственный медицинский университет

Teaching fellow, Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: 100mat23@mail.ru; ORCID ID: https://orcid.org/0009-0001-5505-4677. Author contributions: conducting the research; analyzing and interpreting the obtained data; and participating in scientific design.

Сергей А. Козлов, Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук

Doctor Habil. of Chemical Sciences, Head of the Laboratory of Neuroreceptors and Neuroregulators, M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia; email: serg@ibch.ru; ORCID ID: https://orcid.org/0000-0002-0242-4240. Author contributions: developing the key goals and objectives; critically revising the manuscript, and providing valuable comments.

Загрузки

Опубликован

09.12.2025

Как цитировать

Galenko-Yaroshevsky PA, Zelenskaya AV, Suzdalev KF, Chuyan EN, Ravaeva MY, Murashko RA, Vassiliev PM, Glechyan TR, Sergeeva AV, Leychenko EV, Chubinskiy-Nadezhdin VI, Gulevskaya ON, Korolkova YV, Shamatova MM, Vasileva VY, Ishkhanyan NN, Kozlov SA (2025) Analgesic activity of imidazo[1,2-a]indole derivative and its involvement of TRPV1 and κ-opioid receptors. Research Results in Pharmacology 11(4): 17–37. https://doi.org/10.18413/rrpharmacology.11.641

Выпуск

Том 11 № 4 (2025)

Раздел

Экспериментальная фармакология

Лицензия

Copyright (c) 2025 Galenko-Yaroshevsky PA, Zelenskaya AV, Suzdalev KF, Chuyan EN, Ravaeva MYu, Murashko RA, Vassiliev PM, Glechyan TR, Sergeeva AV, Leychenko EV, Chubinsky-Nadezhdin VI, Gulevskaya ON, Korolkova YuV, Shamatova MM, Vasileva VYu, Ishkhanyan NN, Kozlov SA

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