Значение количественной ЭЭГ в интерпретации бензодиазепинового теста у больных в вегетативном состоянии

Using the multiparameter method of EEG analysis with a complex study of coherent interband links with topographic mapping and localization of equivalent dipole sources of individual EEG components, characteristic signs of changes in intercentral neuronal connections at different stages of a vegetative state were obtained, features of structural and functional interrelations for patients in a vegetative state in benzodiazepine test interpretation of which identification can represent and interest for the output prediction and selection of adequate therapy.Основной целью проведения бензодиазепинового теста у больных в вегетативном состоянии является поиск прогностически значимых показателей ЭЭГ для оценки функционального состояния мозга. С использованием многопараметрического метода анализа ЭЭГ с комплексным исследованием когерентных межзональных связей с топографическим картированием и локализацией эквивалентных дипольных источников отдельных ЭЭГ-составляющих получены характерные признаки изменений межцентральных нейрональных связей, на разных стадиях вегетативного состояния, получены характерные признаки изменений межцентральных нейрональных связей характерных для вегетативного состояния на фоне болюсного введения диазепама

Противосудорожное действие производного 4-бензоил-пиридина (ГИЖ-298) на пароксизмальную активность в структурах мозга крыс с кобальт-индуцированной очаговой эпилепсией на первой стадии формирования эпилептической системы

He aim of the study was to investigate the influence of a derivative of 4-benzoyl pyridine connection, GIZ-298 on electroencephalographic manifestations ranvulsive activity in the brain structures of rats with cobalt-induced focal epilepsy in the first stage of the formation of epileptic system. Methodology of the study. We used the technique of creation (by an application of cobalt to the brain of rats) chronic epileptogenic focus, generating paroxysmal activity in different brain structures: the ipsi- and contralateral cortex, hippocampus and hypothalamus. The results of the study. Established that injection ofGIZ-298 at a dose of 60 mg/kg (intraperitoneally, once) on the first stage of development of the system eliminates epileptic EEG manifestations of seizure activity in all the investigated structures of the brain, with the greatest efficiency in the ipsilateral cortex and the hypothalamus, significantly reducing both the number and duration of seizure discharges.Целью исследования явилось изучение влияния производного 4-бензоил пиридина - соединения ГИЖ-298 на электроэнцефалографические проявления судорожной активности в структурах мозга крыс с кобальт-индуцированной очаговой эпилепсией на первой стадии формирования эпилептической системы. Методика исследования. Использовалась методика создания (путём аппликации кобальта на кору мозга крыс) хронического эпилептогенного очага, генерирующего пароксизмальную активность в различных структурах мозга: ипси- и контрлатеральной коре, гиппокампе и гипоталамусе. Результаты исследования. Установлено, что соединение ГИЖ-298 в дозе 60 мг/кг (внутрибрюшинно, однократно) на первой стадии развития эпилептической системы устраняет электроэнцефалографические проявления судорожной активности во всех исследуемых структурах мозга, с наибольшей эффективностью в ипсилатеральной коре и гипоталамусе, статистически достоверно уменьшая как число, так и длительность судорожных разрядов

Роль 3-оксиметаболита феназепама и леваны в реализации их нейротропного действия

Work is devoted to a comparative analysis of the pharmacological action and integral indicators pharmacokinetics of 1,4- benzodiazepine - phenazepam and levan, as well as their total active 3-oximetabolite formed by different mechanisms. It is shown that in the tests levan antagonism corazolum and thiosemicarbazide inferior phenazepam anticonvulsant activity, but surpasses phenazepam on activity in the maximal electroshock test and has a lower severity miorelaxation action. Comparison effects of phenazepam and levad with effects of 3-oximetabolite indicate greater similarity effects than metabolite with phenazepam. With the use of radiolabeled compounds were established change in the ratio of the areas under the concentration curve 3-oximetabolite in the brain and blood when administered phenazepam (AUCbrain / AUCblood = 0,96 ± 0,27) or levan (AUCbrain / AUCblood = 1,4 ± 0,1). This fact is associated with different ways of biotransformation: oxidative hydroxylation of phenazepam CYP450 and nonspecific carboxylesterase hydrolysis of levan, which explains the difference in the pharmacological effect of the test compounds.Работа посвящена сравнительному анализу фармакологического действия и интегральных показателей фармакокинетики производных 1,4-бенздиазепина - феназепама и леваны, а также их общего активного 3-оксиметаболита, образующегося различными механизмами. Показано, что левана в тестах антагонизма с коразолом и тиосемикарбазидом уступает по противосудорожной активности феназепаму, но превосходит феназепам по активности в тесте максимального электрошока и имеет меньшую выраженность миорелаксантного действия. Сопоставление эффектов феназепама и левады с эффектами 3-оксиметаболита свидетельствует о большем сходстве эффектов метаболита с феназепамом. С использованием радиоактивно меченых соединений установлено изменение соотношения площадей под концентрационными кривыми 3-оксиметаболита в мозгу и крови при введении феназепама (AUC /AUC = 0,96 ± 0,27) или леваны (AUC /AUC = 1,4 ± 0,1). Данный факт связан с различными путями биотрансформации: окислительное гидроксилирование феназепама P450 и гидролиз неспецифическими карбоксилэстеразами леваны, что и обуславливает отличие в фармакологическом действии исследуемых соединений

Новое производное оксимов 4-бензоилпиридинов ГИЖ-298, обладающее противосудорожной активностью

Novel derivative of benzoylpyridine oximes - GIZH-298 (4-benzoylpyridine 0-(2-morpholinoethyl) oxime oxalate) was designed and synthesized in this work. This compound has a broad spectrum of anticonvulsant effects, eliminating primary generalized seizures in maximal electroshock (MES) and corazol antagonism tests in rodents in the doses of 0,5-100 mg/kg. LD50 for compound GIZH-298 is 316 mg/kg intraperitoneally (mouse). GIZH-298 has a large therapeutic breadth.В настоящей работе осуществлён дизайн и синтез нового производного оксима 4-бензоилпиридина - ГИЖ-298 (оксалат 0-(2-морфолиноэтил)оксима 4-бензоилпиридина). Это соединение обладает противосудорожной активностью, устраняя первично-генерализованные судороги в тестах антагонизма с максимальным электрошоком (МЭШ) и коразолом в дозах 0,5-100 мг/кг у грызунов внутрибрюшинно. ЛД50 при внутрибрюшинном введении для соединения ГИЖ-298 составляет 316 мг/кг (мыши). Таким образом, ГИЖ-298 имеет большую терапевтическую широту

Research and development of 2-ethyl-6-methyl-3-oxypyridine succinate nano-form for the treatment of epilepsy

The aim is to develop an antiepileptic drug based on polymer nanoparticles with 2-ethyl-6-methyl-3-oxypyridine succinate to facilitate the drug transport through the blood-brain barrier.Materials and methods. The nano-drug was created using the biologically active substance 2-ethyl-6-methyl-3-hydroxypyridine succinate and polybutyl cyanoacrylate (PBCA) nanoparticles. The advantages of this nano-form over the active ingredient of the same drug were studied using experimental models: the maximum electroshock test (MES), the antagonism test with corazol, models with a cobaltinduced epileptic focus and secondary generalized convulsions, and models of status epilepticus.Results. The antiseizure effects of the nanoform on the experimental models of epilepsy are identified.Conclusion. The nano-drug reduces the number of secondary generalized clonic-tonic seizures by 7.8 times; it also reduces 10-fold the animal mortality and diminishes the seizure manifestations that occur in the interictal period of the epileptic status

NEW BIOMOLECULAR TARGETS FOR ANTIEPILEPTIC DRUGS

The review presents data on new antiepileptic drugs (AEDs), which have been applied in medical practice in recent years. New AEDs have different spectrum of pharmacological effects and mechanism of action. The authors presented the classification of AEDs for their ability to influence the processes of excitation and inhibition in the central nervous system. This article contains information about AEDs, blocking or modifying the ionic conductivity of the voltagedependent Na+ and Ca++-channels; AEDs, blocking glutamate receptors; AEDs, activating the ionic conductivity of K+ channels; AEDs, enhancing the braking effect of GAB

Effect of lacosamide on epileptiform activity and structure-function relations in the brain of rats with chronic focal epilepsy

The aim was to study the effect of lacosamide on epileptiform activity (EрA) and structure-function relations in the brain in the course of development of the epileptic system in rats with cobalt-induced chronic epilepsy. Materials and methods. To model chronic focal epilepsy, we used topical applications of cobalt on the sensorimotor zone of the rat cortex. The effect of lacosamide (20 mg/kg) on the cobalt-induced epileptiform activity was analyzed in parallel with with the monitoring of spectral-coherent changes in the brain during the development of the epileptic system (ES). Results. In the first 30 minutes after the administration, lacosamide briefly enhanced the EрA in the hippocampus and ipsilateral cortex, and also strengthened the cortical-hippocampal (at stage 1) and cortical-hypothalamic connections (at stage 2). Two hours after the drug administration, a decrease in EрA was observed at stages 1 and 2 of the ES development, especially in the contralateral cortex and hippocampus. At all frequency ranges, the level of the inter-center connections decreased (most pronounced in the cortical-hippocampal links). Conclusion. The effect of lacosamide on EрA in the rat brain with cobalt-induced epileptogenic focus is characterized by a decrease in EрA, two hours after the drug administration. This effect is most expressed in the cortex and hippocampus, and is accompanied by a decrease in the level of the corticalhippocampal connections

COMPARATIVE ANTICONVULSANT AND ANTIHYPOXIC EFFECTS OF ASTROKS AND MEXIDOL IN INJECTABLE FORM AND 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE SUCCINATE SUBSTANCE

The purpose of this study was to examine in experiment anticonvulsant and antihypoxic action of 2-ethyl-6-methyl-3-hydroxypyridine succinate medications — Astroks in injectable form (vial of 100 mg in 2 ml) compared with Mexidol injectable form (vial of 100 mg in 2 ml) and the substance 2-ethyl-6- methyl-3-hydroxypyridine succinate (EMHPS). Materials and methods. Simulation of primary generalized eizures was performed using the maximal electroshock (MES) and pentylenetetrazole injection. Antihypoxic effects of drugs was studied on the model of normobaric hypoxia with hypercapnia.Results: it was found that astroks injection at a dose of 200 mg/kg has a similar antihypoxic and anticonvulsant efficacy with EMHPS substance. Compared to injectable form of Meksidol astroks has similar efficacy in the test of antagonism with MES. Astroks exceeds the effect of Mexidol in the test of antagonism with pentylenetetrazole and has more severe antihypoxic action.Conclusion. Аstroks injectable has pronounced antihypoxic and anticonvulsant action in the experiment which have some advantages over injectable Meksidol

EFFECTS OF LEVETINOL ON EPILEPTIFORM ACTIVITY OF THE BRAIN IN RATS WITH COBALT-INDUCED EPILEPSY

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

POSSIBILITIES OF APPLICATION THE PROLONGED FORM VALPROIC ACID AND ANTIOXIDANT IN SECONDARYGENERALIZED SEIZURES (clinical and experimental investigation)

Possibilities of application the prolonged form valproic acid and antioxidant in secondary - generalized seizures was investigated in experiment and in clinical study in patients with epilepsy. In rats with cobalt-induced epilepsy their efficacy has been revealed by the suppression of determinant hearth in the cortex, which is as a hypothalamus the leading focus for the developing epileptic system in forming of secondary - generalized seizers. Depakine Chronosphere statistically significantly surpasses Depakine Chrono in activity of removal epileptiform discharges in electrocorticogrammes it was determined optimal daily dose of antioxidant Mexidol and interval between the taking of Depakine Chronosphere and injection of antioxidant. Combination of antioxidant and anticonvulsant promotes greater control of seizures in patients with focal symptomatic and/or cryptogenic epilepsy