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The aim of this study was to evaluate the anti-seizure effect of Levetinol tablet (Geropharm) on the cobalt-induced chronic epilepsy.

Materials and methods. A model of cobalt-induced epilepsy was created by applying cobalt powder to the sensorimotor zone of the rat cortex. The effects of Levetinol were studied at the early stage of the epileptic system (ES) formation (on day 2 after the cobalt application), and then at the stage of fully developed ES (on day 6 after the cobalt application).

Results. The present study showed that at the early stage of ES development, Levetinol at doses of 50 and 200 mg/kg had no statistically significant effect on the development of paroxysmal activity in both primary and secondary epileptic foci: in the ipsi- and contralateral cortex, hypothalamus and hippocampus. On day 6 of the cobalt-induced epilepsy, a significant suppression of paroxysmal activity in the above structures of the brain was observed with the administration of Levetinol at a dose of 200 mg/kg. The most pronounced anti-seizure effect was found in the hippocampus; that was expressed in normalization of the bioelectrical activity and appearance of the regular theta rhythm.

Conclusion. The effects of Levetinol are largely manifested in the hippocampal foci of epileptiform activity and, to a lesser extent, in the cortical foci. 

About the Authors

S. A. Litvinova
V.V. Zakusov Institute of Pharmacology
Russian Federation
8 Baltijskaja Str., 125315 Moscow

T. A. Voronina
V.V. Zakusov Institute of Pharmacology
Russian Federation
8 Baltijskaja Str., 125315 Moscow

L. N. Nerobkova
V.V. Zakusov Institute of Pharmacology
Russian Federation
8 Baltijskaja Str., 125315 Moscow

I. S. Kutepova
V.V. Zakusov Institute of Pharmacology
Russian Federation
8 Baltijskaja Str., 125315 Moscow

G. G. Avakyan
N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
1 Ostrovityanova Str., Moscow 117997

G. N. Avakyan
N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
1 Ostrovityanova Str., Moscow 117997


1. De Smedt T., Raedt R., Vonck K., Boon P. Levetiracetam: part II, the clinical profile of a novel anticonvulsant drug. CNS Drug Rev. 2007; 13: 57-78.

2. Gower A. J., Hirsch E, Boehrer A et al. Effects of Levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy. Epilepsy Res. 1995; 22 (3): 207-13.

3. Klitgaard H., Matagne H., Gobert J., Wulfert E. Evidence for a unique profile of Levetiracetam in rodent models of seizures and epilepsy. Eur. J. Pharmacol. 1998; 353: 191-206.

4. Raevskii K.S., Malikova L.A., Kalinin V.V. Ek sperimental’naya i klinicheskaya farmakologiya (in Russian). 2007; 70 (2): 70-74.

5. Loscher W., Hönack D., Rundfeldt C. Antiepileptogenic effects of the novel anticonvulsant Levetiracetam (ucb L059) in the kindling model of temporal lobe epilepsy. J. Pharmacol. Exp. Ther. 1998; 284 (2): 474-9.

6. Mohanraj R., Parker P.G., Stephen L. J., Brodie M. J. Levetiracetam in refractory epilepsy: a prospective obsevational study. Seizure. 2005; 14: 23-27.

7. Palma E., Ragozzino D., Di Angelantonio S., Mascia A. et al. The antiepileptic drug levetiracetam stabilizes the human epileptic GABAA receptors upon repetitive activation. Epilepsia. 2007; 48: 1842-49.

8. Rigo J.M., Hans G., Nguyen L., et al. The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents. Br J Pharmacol. 2002; 136: 659-672.

9. Wakita M., Kotani N., Kogure K., Akaike N. Inhibition of excitatory synaptic transmission in hippocampal neurons by levetiracetam involves Zn²-dependent GABA type A receptor-mediated presynaptic modulation. J Pharmacol Exp Ther. 2014; 348 (2): 246-59.

10. Gillard M., Fuks B., Michel P., Vertongen P., Massingham R., Chatelain P. Binding characteristics of [3H]ucb 30889 to levetiracetam binding sites in rat brain. Eur J Pharmacol. 2003; 478: 1-910.1016.

11. Gillard M., Chatelain P., Fuks B. Binding characteristics of levetiracetam to synaptic vesicle protein 2A (SV2A) in human brain and in CHO cells expressing the human recombinant protein. Eur J Pharmacol. 2006; 536: 102-810.

12. Lynch B.A., Lambeng N., Nocka K., Kensel-Hammes P. et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA. 2004; 101: 9861-610.

13. Rainer S., Volynski K. E., Walker M.C. Is Levetiracetam Different from Other Antiepileptic Drugs? Levetiracetam and its Cellular Mechanism of Action in Epilepsy Revisited. Ther Adv Neurol Disord. 2008; 1(1): 13-24.

14. Stephen L. J., Kelly K., Parker P., Brodie M. J. Levetiracetam monotherapyoutcomes from an epilepsy clinic. Seizure. 2011; 20 (7): 554-7.

15. Bialer M., Johannessen S. I., Levy R.H., Perucca E., Tomson T., White H.S. Progress report on new antiepileptic drugs: a summary of the Tenth Eilat Conference (EILAT X). Epilepsy Res. 2010; 92: 89-12.

16. Angehagen M., Margineanu D.G., BenMenachem E., Rönnbäck L., Hansson E., Klitgaard H. Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons. Neuroreport. 2003; 14: 471-475

17. Carunchio I., Pieri M., Ciotti M. T., Albo F., Zona C. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia. 2007; 48: 654-662.

18. Cataldi M., Lariccia V., Secondo A., di Renzo G., Annunziato L. The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]I increase induced by ATP and bradykinin in PC12 cells. J Pharmacol Exp Ther. 2005; 313: 720-730.

19. Löscher W., Hönack D. Development of tolerance during chronic treatment of kindled rats with the novel antiepileptic drug levetiracetam. Epilepsia. 2000; 41: 1499-1506.

20. Zhang Z. J., Xing G.Q., Russell S., Obeng K., Post R.M. Unidirectional cross-tolerance from levetiracetam to carbamazepine in amygdala-kindled seizures. Epilepsia. 2003; 44 (12): 1487-93.

21. Van Vliet E.A., van Schaik R., Edelbroek P.M. et al. Development of tolerance to levetiracetam in rats with chronic epilepsy. Epilepsia. 2008; 49 (7): 1151-9.

22. Friedman D., French J.A. Effects of intermittent levetiracetam dosing in a patient with refractory daily seizures. Neurology. 2006 Feb 28; 66 (4): 590-1.

23. Packer R.M.A., Nye G., Porter S. E., Volk H.A. Assessment into the usage of levetiracetam in a canine epilepsy clinic. BMC Veterinary Research. 2015; 11: 25.

24. Avakyan G.N., Nerobkova L.N., Voronina T.A., Markina N.V., Mitrofanov A. A. Eksperimental’naya i klinicheskaya farmakologiya (in Russian). 2002; 2: 7-10.

25. Bregman F., Le Saux S., Trottier P., Chauvel L., Maurin Y. Chronic Cobaltinduced Epilepsy: Noradrenaline Ionophoresis and Adrenoceptor Binding Studies in the Rat Cerebral Cortex. J. Neural Transmission. 1985; 63: 109-118.

26. Voronina T.A., Stoĭko M. I., Nerobkova L.N., Avakian G.N., Kraĭneva V.A. Effect of phenytoin on neurotoxin homocysteine thiolactone-induced convulsions and epileptic status in rats with cobalt-induced epilepsy. Eksp Klin Farmakol (in Russian). 2002; 65 (1): 15-8.

27. Walton N.Y., Treiman D.M. Efficacy of ACC-9653 (a phenytoin prodrug) in experimental status epilepticus in the rat. Epilepsy Res. 1990; 5 (2): 165-8.

28. Walton N.Y., Treiman D.M. Valproic acid treatment of experimental status epilepticus. Epilepsy Res. 1992; 12 (3): 199-205.

29. Walton N.Y., Jaing Q., Hyun B., Treiman D.M. Lamotrigine vs. phenytoin for treatment of status epilepticus: comparison in an experimental model. Epilepsy Res. 1996; 24 (1): 19-28.

30. Voronina T.A., Nerobkova L.N. Methodical instructions for the study of anticonvulsant activity of pharmacological substances. A guide to preclinical drug research [Metodicheskie ukazaniya po izucheniyu protivosudorozhnoi aktivnosti farmakologicheskikh veshchestv. Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv (in Russian)]. Moscow. 2012; 1 (14): 235-250.

31. Buresh Dzh., Petran’ M., Zakhar D. Electrophysiological methods of research in biology [Elektrofiziologicheskie metody issledovaniya v biologii (in Russian)]. Moscow. 1964; 551.

Supplementary files

For citation: Litvinova S.A., Voronina T.A., Nerobkova L.N., Kutepova I.S., Avakyan G.G., Avakyan G.N. EFFECTS OF LEVETINOL ON EPILEPTIFORM ACTIVITY OF THE BRAIN IN RATS WITH COBALT-INDUCED EPILEPSY. Epilepsia and paroxyzmal conditions. 2018;10(1):52-62. https://doi.org/10.17749/2077-8333.2018.10.1.052-062

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