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Comparison of effects and electrophysiological mechanisms of action of valproic acid and levetyracetam in an experimental model of focal epilepsy
- Authors: Litvinova S.A.1, Avakyan G.G.2, Voronina T.А.1, Gaidukov I.O.1, Nerobkova L.N.1, Kutepova I.S.1, Avakyan G.N.2
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Affiliations:
- Research Zakusov Institute of Pharmacology
- Pirogov Russian National Research Medical University
- Issue: Vol 12, No 3 (2018)
- Pages: 45-53
- Section: Original articles
- URL: https://www.annaly-nevrologii.com/journal/pathID/article/view/536
- DOI: https://doi.org/10.25692/ACEN.2018.3.6
- ID: 536
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Abstract
Introduction. Despite rapid development of the antiepileptic pharmaceuticals market, about 2/3 of patients suffering from epilepsy do not receive adequate treatment, which is partly due to the variety of mechanisms for the development of epileptic seizures
Objective. А comparative study of the electrophysiological mechanisms of action and effects of valproic acid (Depakin Chrono) and levetiracetam (Levetinol) under experimental focal epilepsy and status epilepticus (SE) in rats.
Materials and methods. Focal chronic epilepsy was caused by the application of cobalt to the sensorimotor cortex. On the 7th–8th day, SE was modeled by the injection of homocysteine, which provoked the development of secondary generalized tonic-clonic seizures.
Results. Levetiracetam had a suppressing effect on the paroxysmal activity of the rat brain only under conditions of a stable SE on the 5th–6th day after the application of cobalt. Its most prominant effect was seen in the hippocampus and was characterized by a significant decrease in epileptic activity (EpiA) in this structure and in the maintenance of a regular rhythm. Valproic acid significantly suppressed EpiA in the ipsilateral cortex, hippocampus and hypothalamus at a stable stage of EpiS development, with the most pronounced effect on the primary cortical focus and hypothalamus. In the model of SE caused by the injection of homocysteine, levetiracetam was ineffective, whereas valproic acid decreased the severity of paroxysmal activity in all the studied structures, especially in the cortex (ipsi- and contralateral, 33 times) and hypothalamus (28 times), which was accompanied by suppression of generalized motor manifestations and reduced number of animal deaths.
Conclusion. In the model of focal cobalt-induced epilepsy, the hippocampus is the leading structure and the target of the levetiracetam action, while the effect of valroic acid is executed through the inhibitory effect on the cortical foci of EpiA and the hypothalamus, which may be main feature in its ability to suppress the SE.
About the authors
Svetlana A. Litvinova
Research Zakusov Institute of Pharmacology
Author for correspondence.
Email: sa_litvinova@mail.ru
Russian Federation, Moscow
Georgii G. Avakyan
Pirogov Russian National Research Medical University
Email: sa_litvinova@mail.ru
Russian Federation, Moscow
Tatyana А. Voronina
Research Zakusov Institute of Pharmacology
Email: sa_litvinova@mail.ru
Russian Federation, Moscow
Igor O. Gaidukov
Research Zakusov Institute of Pharmacology
Email: sa_litvinova@mail.ru
Russian Federation, Moscow
Lyubov N. Nerobkova
Research Zakusov Institute of Pharmacology
Email: sa_litvinova@mail.ru
Russian Federation, Moscow
Inga S. Kutepova
Research Zakusov Institute of Pharmacology
Email: sa_litvinova@mail.ru
Russian Federation, Moscow
Gagik N. Avakyan
Pirogov Russian National Research Medical University
Email: sa_litvinova@mail.ru
Russian Federation, Moscow
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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).