Analgesic activity of new ligands of the NMDA receptor complex
- Authors: Yakovleva E.E.1, Kamalova M.T.1, Brusina M.A.1, Bychkov E.R.1, Piotrovskiy L.B.1, Shabanov P.D.1
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Affiliations:
- Institute of Experimental Medicine
- Issue: Vol 22, No 2 (2024)
- Pages: 171-178
- Section: Original study articles
- URL: https://journals.rcsi.science/RCF/article/view/263146
- DOI: https://doi.org/10.17816/RCF624859
- ID: 263146
Cite item
Abstract
BACKGROUND: The activation of spinal cord NMDA receptors is a key factor in the pathogenesis of acute and chronic pain. Therefore, the use of existing NMDA antagonists in analgesic schemes and the development of new compounds targeting the NMDA receptor complex are gaining attention. New ligands of the glutamate NMDA receptor complex are derivatives of imidazole-4,5-dicarboxylic acid. The conformational rigidity of the molecules of imidazole-4,5-dicarboxylic acid derivatives allows for increased selectivity of interaction and reduced side effects.
AIM: This study aimed to investigate the analgesic effect of new ligands of the glutamate NMDA receptor complex, which are derivatives of imidazole-4,5-dicarboxylic acid, in rats using the tail-flick test and the formalin test.
MATERIALS AND METHODS: The analgesic activity of the compounds was examined in a model of acute somatic (thermal) pain in the tail-flick test and model of somatic pain induced by algogens in the formalin test. The tested compounds (IEM-303 and IEM-2044) were administered intraperitoneally at doses of 5, 10, 15, and 20 mg/kg. Мetamizole was used as the comparison drug.
RESULTS: The experiments demonstrated a significant dose-dependent analgesic effect of the tested compounds on the experimental models of acute pain at doses of 5–20 mg/kg. The tail-flick latency increased by 1.4–1.7 times in the IEM-2044 and IEM-303 groups compared with the value in the control group.
CONCLUSIONS: The analgesic activity of the tested compounds at 10–20 mg/kg doses was comparable to that of metamizole, indicating the prospect of developing these agents and further searching for effective and safe analgesics in this pharmacological class.
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##article.viewOnOriginalSite##About the authors
Ekaterina E. Yakovleva
Institute of Experimental Medicine
Author for correspondence.
Email: sampuria@yandex.ru
ORCID iD: 0000-0002-0270-0217
SPIN-code: 6728-7340
Cand. Sci. (Medicine)
Russian Federation, Saint PetersburgMekhriniso T. Kamalova
Institute of Experimental Medicine
Email: tkamalova@mail.ru
Russian Federation, Saint Petersburg
Mariia A. Brusina
Institute of Experimental Medicine
Email: mashasemen@gmail.com
ORCID iD: 0000-0001-8433-120X
SPIN-code: 8953-8772
Cand. Sci. (Chemistry)
Russian Federation, Saint PetersburgEvgenii R. Bychkov
Institute of Experimental Medicine
Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN-code: 9408-0799
Dr. Sci. (Medicine)
Russian Federation, Saint PetersburgLevon B. Piotrovskiy
Institute of Experimental Medicine
Email: piotrovsky@yandex.ru
ORCID iD: 0000-0001-8679-1365
SPIN-code: 2927-6178
Dr. Sci. (Biology), Professor
Russian Federation, Saint PetersburgPetr D. Shabanov
Institute of Experimental Medicine
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477
Dr. Sci. (Medicine), Professor
Russian Federation, Saint PetersburgReferences
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