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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">epilepsia</journal-id><journal-title-group><journal-title xml:lang="en">Epilepsy and paroxysmal conditions</journal-title><trans-title-group xml:lang="ru"><trans-title>Эпилепсия и пароксизмальные состояния</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2077-8333</issn><issn pub-type="epub">2311-4088</issn><publisher><publisher-name>IRBIS LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.17749/2077-8333.2018.10.1.052-062</article-id><article-id custom-type="elpub" pub-id-type="custom">epilepsia-392</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>EXPERIMENTAL EPILEPTOLOGY</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНАЯ ЭПИЛЕПТОЛОГИЯ</subject></subj-group></article-categories><title-group><article-title>EFFECTS OF LEVETINOL ON EPILEPTIFORM ACTIVITY OF THE BRAIN IN RATS WITH COBALT-INDUCED EPILEPSY</article-title><trans-title-group xml:lang="ru"><trans-title>ОСОБЕННОСТИ ДЕЙСТВИЯ ЛЕВЕТИНОЛА НА РАЗВИТИЕ СУДОРОЖНОЙ АКТИВНОСТИ У КРЫС С КОБАЛЬТ-ИНДУЦИРОВАННОЙ ХРОНИЧЕСКОЙ ЭПИЛЕПСИЕЙ</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9139-2334</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Литвинова</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Litvinova</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., ведущий научный сотрудник лаборатории психофармакологии, </p><p>ул. Балтийская, 8, 125315 Москва</p></bio><bio xml:lang="en"><p>8 Baltijskaja Str., 125315 Moscow</p></bio><email xlink:type="simple">sa_litvinova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Воронина</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Voronina</surname><given-names>T. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>профессор, д.м.н., руководитель лаборатории психофармакологии,</p><p>ул. Балтийская, 8, 125315 Москва</p></bio><bio xml:lang="en"><p>8 Baltijskaja Str., 125315 Moscow</p></bio><email xlink:type="simple">voroninata38@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Неробкова</surname><given-names>Л. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Nerobkova</surname><given-names>L. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., старший научный сотрудник лаборатории психофармакологии,</p><p>ул. Балтийская, 8, 125315 Москва</p></bio><bio xml:lang="en"><p>8 Baltijskaja Str., 125315 Moscow</p></bio><email xlink:type="simple">Ln_Nerobkova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кутепова</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Kutepova</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>аспирант,</p><p>ул. Балтийская, 8, 125315 Москва</p></bio><bio xml:lang="en"><p>8 Baltijskaja Str., 125315 Moscow</p></bio><email xlink:type="simple">shatalovo.100@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Авакян</surname><given-names>Г. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Avakyan</surname><given-names>G. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., ассистент кафедры неврологии, нейрохирургии и медицинской генетики,</p><p>ул. Островитянова, 1, Москва 117997</p></bio><bio xml:lang="en"><p>1 Ostrovityanova Str., Moscow 117997</p></bio><email xlink:type="simple">avakyan_georgy@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Авакян</surname><given-names>Г. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Avakyan</surname><given-names>G. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор кафедры неврологии, нейрохирургии и медицинской генетики,</p><p>ул. Островитянова, 1, Москва 117997</p></bio><bio xml:lang="en"><p>1 Ostrovityanova Str., Moscow 117997</p></bio><email xlink:type="simple">gavakyan@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное научное учреждение «НИИ Фармакологии им. В.В. Закусова»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>V.V. Zakusov Institute of Pharmacology</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N. I. Pirogov Russian National Research Medical University, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>31</day><month>05</month><year>2018</year></pub-date><volume>10</volume><issue>1</issue><fpage>52</fpage><lpage>62</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Litvinova S.A., Voronina T.A., Nerobkova L.N., Kutepova I.S., Avakyan G.G., Avakyan G.N., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Литвинова С.А., Воронина Т.А., Неробкова Л.Н., Кутепова И.С., Авакян Г.Г., Авакян Г.Н.</copyright-holder><copyright-holder xml:lang="en">Litvinova S.A., Voronina T.A., Nerobkova L.N., Kutepova I.S., Avakyan G.G., Avakyan G.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.epilepsia.su/jour/article/view/392">https://www.epilepsia.su/jour/article/view/392</self-uri><abstract><p>The aim of this study was to evaluate the anti-seizure effect of Levetinol tablet (Geropharm) on the cobalt-induced chronic epilepsy.</p><sec><title>Materials and methods</title><p>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).</p></sec><sec><title>Results</title><p>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.</p></sec><sec><title>Conclusion</title><p>Conclusion. The effects of Levetinol are largely manifested in the hippocampal foci of epileptiform activity and, to a lesser extent, in the cortical foci. </p></sec></abstract><trans-abstract xml:lang="ru"><p>Целью исследования явилось изучение противосудорожного эффекта таблетированной лекарственной формы препарата Леветинола (Герофарм) на модели кобальт-индуцированной хронической эпилепсии.</p><sec><title>Материалы и методы</title><p>Материалы и методы. Модель кобальт-индуцированной эпилепсии вызывали аппликацией кобальта на сенсомоторную зону коры крысы. Эффекты Леветинола изучали на начальной стадии развития эпилептической системы (ЭС) – 2-й день после аппликации кобальта и на фоне генерализации пароксизмальной активности – 6-й день после аппликации кобальта.</p></sec><sec><title>Результаты</title><p>Результаты. проведенные исследования показали, что в начальной стадии развития ЭС Леветинол в дозах 50 и 200 мг/кг не оказывал статистически достоверного влияния на развитие пароксизмальной активности как в первичных, так и во вторичных эпилептических очагах: в ипси-, контралатеральной коре, гипоталамусе и гиппокампе. Значительное подавление пароксизмальной активности во всех исследуемых структурах мозга крыс с кобальтовой эпилепсией наблюдалось при введении Леветинола в дозе 200 мг/кг на 6-й день развития ЭС. При этом наибольшая выраженность противосудорожного эффекта проявлялась в гиппокампограммах, что выражалось в нормализации биоэлектрической активности и появлении регулярного тета-ритма.</p></sec><sec><title>Заключение</title><p>Заключение. Эффекты Леветинола в большей степени направлены на гиппокампальные очаги эпилептиформной активности и в меньшей степени – на корковые очаги. </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>леветирацетам</kwd><kwd>Леветинол</kwd><kwd>эпилепсия</kwd><kwd>ЭЭГ</kwd><kwd>пароксизмальная активность</kwd><kwd>кобальт-индуцированная эпилепсия</kwd><kwd>крысы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Levetiracetam</kwd><kwd>Levetinol</kwd><kwd>epilepsy</kwd><kwd>seizures</kwd><kwd>EEG</kwd><kwd>paroxysmal activity</kwd><kwd>cobalt-induced epilepsy</kwd><kwd>rats</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Раевский К.С., Маликова Л.А., Калинин В.В. Нейрональные и нейрохимические механизмы действия нового противоэпилептического средства леветирацетама. Экспериментальная и клиническая фармакология. 2007; 70 (2): 70-74.</mixed-citation><mixed-citation xml:lang="en">Raevskii K.S., Malikova L.A., Kalinin V.V. Ek sperimental’naya i klinicheskaya farmakologiya (in Russian). 2007; 70 (2): 70-74.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Mohanraj R., Parker P.G., Stephen L. J., Brodie M. J. Levetiracetam in refractory epilepsy: a prospective obsevational study. Seizure. 2005; 14: 23-27.</mixed-citation><mixed-citation xml:lang="en">Mohanraj R., Parker P.G., Stephen L. J., Brodie M. J. Levetiracetam in refractory epilepsy: a prospective obsevational study. Seizure. 2005; 14: 23-27.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Stephen L. J., Kelly K., Parker P., Brodie M. J. Levetiracetam monotherapy-outcomes from an epilepsy clinic. Seizure. 2011; 20 (7): 554-7.</mixed-citation><mixed-citation xml:lang="en">Stephen L. J., Kelly K., Parker P., Brodie M. J. Levetiracetam monotherapyoutcomes from an epilepsy clinic. Seizure. 2011; 20 (7): 554-7.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">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</mixed-citation><mixed-citation xml:lang="en">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</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Löscher W., Hönack D. Development of tolerance during chronic treatment of kindled rats with the novel antiepileptic drug levetiracetam. Epilepsia. 2000; 41: 1499-1506.</mixed-citation><mixed-citation xml:lang="en">Löscher W., Hönack D. Development of tolerance during chronic treatment of kindled rats with the novel antiepileptic drug levetiracetam. Epilepsia. 2000; 41: 1499-1506.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Авакян Г.Н., Неробкова Л.Н., Воронина Т.А., Маркина Н.В., Митрофанов А.А. Влияние карбамазепина на структурно функциональные связи в развитии эпилептической системы. Экспериментальная и клиническая фармакология. 2002; 2: 7-10.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">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. 2002; 65 (1): 15-8.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Walton N.Y., Treiman D.M. Valproic acid treatment of experimental status epilepticus. Epilepsy Res. 1992; 12 (3): 199-205.</mixed-citation><mixed-citation xml:lang="en">Walton N.Y., Treiman D.M. Valproic acid treatment of experimental status epilepticus. Epilepsy Res. 1992; 12 (3): 199-205.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">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.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Воронина Т.А., Неробкова Л.Н. Методические указания по изучению противосудорожной активности фармакологических веществ. Руководство по проведению доклинических исследований лекарственных средств. М. 2012; 1 (14): 235-250.</mixed-citation><mixed-citation xml:lang="en">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.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Буреш Дж., Петрань М., Захар Д. Электрофизиологические методы исследования в биологии. М. 1964; 551.</mixed-citation><mixed-citation xml:lang="en">Buresh Dzh., Petran’ M., Zakhar D. Electrophysiological methods of research in biology [Elektrofiziologicheskie metody issledovaniya v biologii (in Russian)]. Moscow. 1964; 551.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
