Analgesic activity of imidazo[1,2-a]indole derivative and its involvement of TRPV1 and κ-opioid receptors

Authors

DOI:

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

Abstract

Introduction: Various analgesics, primarily nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, are used to relieve pain. On the account that opioids can cause respiratory depression, psychological and physical dependence, as well as addiction, and NSAIDs can cause gastro- and enteropathy, nephrotoxicity, bronchospasm, bleeding, and cardiovascular dysfunction, the search for new molecules exerting an analgesic effect through other cellular targets is relevant. The aim of this study was to evaluate the analgesic effect of a new imidazo[1,2-a]indole derivative in various pain models and its effect on TRPV1 and κ-opioid receptors.

Materials and Methods. The median lethal dose (LD50) of the imidazo[1,2-a]indole derivative (lab code SV-1010) was determined in experiments on mice and rats. The analgesic effect of SV-1010 was studied by means of the hot plate test (in mice), tail-flick test (in rats), paw pressure test (in rats), abdominal constriction test (in mice), formalin test (in rats), and neuropathic pain test (in rats). In addition, the effect of SV-1010 on TRPV1 ion channels was examined (in a Chinese hamster ovary cell line with an induced expression of a rat TRPV1 channel), and the potential for κ-opioid receptor activation was tested (by means of molecular docking). SV-1010 and the reference drugs diclofenac, indomethacin, ketorolac, and pregabalin were administered intragastrically.

Results and Discussion: SV-1010 is less toxic than diclofenac, indomethacin, and ketorolac, exhibits a pronounced analgesic effect, but exceeds diclofenac, indomethacin, ketorolac, and pregabalin by the potency and therapeutic index. The treatment sites for SV-1010 to exert its analgesic effect are the supraspinal, supraspinal + peripheral, spinal, and peripheral levels of pain sensitivity. Of note is the high selectivity of SV-1010 to blocking TRPV1 ion channel and activating κ-opioid receptors.

Conclusion: Significantly lower acute toxicity (when compared to such of diclofenac, indomethacin, and ketorolac), high analgesic activity, and a wider therapeutic index (when compared to such of diclofenac, indomethacin, ketorolac, and pregabalin) make SV-1010 promising for further preclinical study.

Graphical Abstract

Keywords:

analgesic effect, imidazo[1,2-a]indole derivative, TRPV1 ion channels, κ-opioid receptors

References

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Author Contribution

Pavel A. Galenko-Yaroshevsky, Kuban State Medical University

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.

Anait V. Zelenskaya, Kuban State Medical University

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.

Konstantin F. Suzdalev, Southern Federal University

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.

Elena N. Chuyan, V.I. Vernadsky Crimean Federal University

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.

Marina Yu. Ravaeva, V.I. Vernadsky Crimean Federal University

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.

Roman A. Murashko, Kuban State Medical University,

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.

Pavel M. Vassiliev

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.

Tereza R. Glechyan, Kuban State Medical University

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.

Alina V. Sergeeva, Kuban State Medical University

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.

Elena V. Leychenko, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences

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.

Vladislav I. Chubinskiy-Nadezhdin, Institute of Cytology, Russian Academy of Sciences

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.

Olga N. Gulevskaya, Kuban State University of Physical Education

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.

Yulia V. Korolkova, M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

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.

Margarita M. Shamatova, M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

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.

Valeria Yu. Vasileva, Institute of Cytology, Russian Academy of Sciences

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.

Narek N. Ishkhanyan, Kuban State Medical University

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.

Sergey A. Kozlov, M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

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.

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Published

09-12-2025

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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

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Vol. 11 No. 4 (2025)

Section

Experimental Pharmacology

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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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