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Post a Comment Studying the anticonvulsive activity of new ligands of NDMA-receptor complex – imidazole-4,5-dicarbonic acid derivatives
- Authors: Jakovleva E.E.1, Foksha S.P.1, Brusina M.A.1, Kubarskaja L.G.1,2, Piotrovskij L.B.1, Bychkov E.R.1,3, Shabanov P.D.1
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Affiliations:
- Institute of Experimental Medicine
- Institute of Toxicology, Federal Medical and Biological Agency
- S.M. Kirov Military Medical Academy
- Issue: Vol 18, No 2 (2020)
- Pages: 149-154
- Section: Original study articles
- URL: https://journal-vniispk.ru/RCF/article/view/42404
- DOI: https://doi.org/10.17816/RCF182149-154
- ID: 42404
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Abstract
NMDA receptors were proven to play a significant role in the processes of epileptogenesis. Experimental data indicate a significant anticonvulsant effect of NMDA receptor antagonists, but the use of the studied NMDA ligands remains limited due to their low efficiency and toxic effects. The aim of the study was to investigate the anticonvulsant effect of new ligands of the glutamate NMDA receptor complex – imidazole-4,5-dicarboxylic acid (IDA) derivatives on a model of NMDA-induced convulsions in mice. The tested agents (IEM2258 and IEM2248) were injected into the lateral ventricles of a waking mouse brain at doses of 0.1–0.5 mmol in 5 µl 15 minutes before the convulsant (NMDA). Valproic acid was used as a comparator drug. The results of the study showed that IDA derivatives exhibit anticonvulsant activity of various degrees of severity. A pronounced anticonvulsant effect was established for IEM2258 at a dose of 0.4 mmol: a significant reduction in the duration of convulsions (compared to the previous dose of the tested substance) and a total absence of NMDA-induced deaths. IEM2248 showed anticonvulsant activity at a dose of 0.2 mmol, in 100% of cases preventing fatal outcomes and completely protecting animals from the convulsions. Thus, the data obtained in this study showed dose-dependent anticonvulsant effect of new IDA derivatives (IEM2258 and IEM2248) due to the blockade of the NMDA receptor complex, that indicates the promising aspect for the development of these agents and further searching for effective and safe anticonvulsants among this pharmacological class.
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##article.viewOnOriginalSite##About the authors
Ekaterina E. Jakovleva
Institute of Experimental Medicine
Author for correspondence.
Email: eeiakovleva@mail.ru
PhD, Scientific Researcher of The Laboratory of Chemistry and Pharmacology of Pharmaceutical Drug of S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgStanislav P. Foksha
Institute of Experimental Medicine
Email: dr.foksha@mail.ru
PhD Student, S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgMarija A. Brusina
Institute of Experimental Medicine
Email: mashasemen@gmail.com
PhD, Junior Scientific Researcher of The Laboratory for the synthesis and nanotechnology of drugs of S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgLarisa G. Kubarskaja
Institute of Experimental Medicine; Institute of Toxicology, Federal Medical and Biological Agency
Email: larkub@yandex.ru
PhD, Leading Engineer, S.V. Anichkov Department of Neuropharmacology; Senior Researcher
Russian Federation, Saint PetersburgLevon B. Piotrovskij
Institute of Experimental Medicine
Email: piotrovsky@yandex.ru
Doctor of Biological Sciences, Professor, Head of The Laboratory for the synthesis and nanotechnology of drugs of S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgEugenii R. Bychkov
Institute of Experimental Medicine; S.M. Kirov Military Medical Academy
Email: bychkov@mail.ru
PhD, Head of The Laboratory of Chemistry and Pharmacology of Pharmaceutical Drugs of S.V. Anichkov Department of Neuropharmacology; Lecturer Department of Pharmacology
Russian Federation, Saint PetersburgPetr D. Shabanov
Institute of Experimental Medicine
Email: pdshabanov@mail.ru
Dr. Med. Sci. (Pharmacology), Professor and Head, Dept. of Neuropharmacology
Russian Federation, Saint PetersburgReferences
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