Abstract—Here we studied the effects of anti-epileptic substance GIZh-298 and the drug of comparison sodium valproate (NaV) on the contents of excitatory and inhibitory amino acids in the frontal cortex, hypothalamus, striatum, and hippocampus of the mouse brain in a model of generalized tonic-clonic seizures induced by maximal electroshock (MES). The levels of excitatory amino acids such as aspartate in the hypothalamus and glutamate in the hippocampus were decreased by 20.8 and 16.7%, respectively, and of inhibitory amino acids, such as glycine, GABA, and taurine were also decreased by 16–20% in average in those structures 5 min after the MES application indicating the exhaustion of aminoacidic neurotransmission. Intragastric administration of NaV at a dose of 200 mg/kg, which causes the anti-seizure effect, prevented the MES-induced decrease in the content of GABA and the GABA/glutamate ratio in the hypothalamus. NaV similarly decreased the aspartate level in the hypothalamus, striatum, and hippocampus in the intact group of mice and in mice after seizures. Intragastric administration of GIZh-298 at a dose of 60 mg/kg prevented the MES-evoked decrease in the GABA/glutamate ratio and the levels of GABA, glycine, and taurine in the hypothalamus.
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This study was performed within the state assignment of Ministry of Education and Science of the Russian Federation FGFG-2022-0004 “Search and development of new treatments for epilepsy, autism spectrum disorders, and Parkinson’s disease” for the Zakusov Research Institute of Pharmacology.
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This study was organized and carried out in accordance with Protocol No. 81 of the Council of the Eurasian Economic Commission dated November 3, 2016 “On Approval of the Rules of Good Laboratory Practice of the Eurasian Economic Union in the field of medicines handling”. The experimental protocol was approved by the Commission on Biomedical Ethics of the Zakusov Research Institute of Pharmacology (protocol no. 7 dated June 7, 2022).
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Narkevich, V.B., Litvinova, S.A., Kasabov, K.A. et al. The Effect of Pyridine Oxime Derivative (GIZh-298) and Sodium Valproate on the Neurotransmitter Amino Acids Content in the Brain Structures of Mice in the Maximal Electroshock Seizure Test. Neurochem. J. 18, 291–295 (2024). https://doi.org/10.1134/S1819712424020107
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DOI: https://doi.org/10.1134/S1819712424020107