Abstract—We studied the effects of the potential antiepileptic agent GIZh-298 and a comparison drug, topiramate, on the concentration of monoamines and their metabolites in the frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocampus in the rat brain after generalized tonic–clonic seizure caused by electroshock (MES). We found that GIZh-298 (60 mg/kg, i.p.) exhibits a pronounced anticonvulsant effect in the test of MES antagonism and prevents the increase in functional activity of the dopaminergic system and the reduction of the norepinephrine (NE) content in the same structure. Topiramate (100 mg/kg, i.p.), as well as the GIZh-298, prevented the emergence of MES-induced seizures and stimulated an increase in the NA level in the striatum to the normal values but did not affect the MES-induced changes in the functional activity of the dopaminergic system of the nigrostriatal system. Therefore, it may be concluded that the modulation of the noradrenergic neurotransmission in the striatum is one of the mechanisms of the anticonvulsant effect of both GIZh-298 and topiramate in the test of MES antagonism and, in addition, GIZh-298, unlike topiramate, contributes to the reduction of the functional activity of the dopaminergic system in this structure in response to MES.

We present here the synthesis of 3- and 4-benzoylpyridine oxime derivatives with potential anticonvulsant action. The most active compound in the maximum electric shock test was 4-benzoylpyridine O-2-morpholinoethyloxime oxalate (1a), i.p. doses of 60 – 150 mg/kg of which increased the survival of mice to 100%. The best effect in the corasol antagonism test was obtained with 4-benzoylpyridine O-(isonicotinoyl)oxime (2c), i.p. doses of 12.5 mg/kg of which increased the survival of mice to 67% and the latent period of onset of generalized tonic-clonic convulsions to 52 sec. Compound 1a had low toxicity (the i.p. LD50 in mice was 316 mg/kg) and a therapeutic index of 21.

The effects of the putative antiepileptic drug GIZh-298 and the reference standard topiramate on the concentrations of monoamines and their metabolites in the frontal cortex, hypothalamus, nucleus accumbens, striatum, and hippocampus of Wistar rats was investigated using HPLC. It was shown that topiramate at a dose of 100 mg/kg induces an increase in dopamine concentration and a decrease in its metabolism rate in the frontal cortex, a decrease in the level of its metabolites in the dorsal striatum, and an increase in concentrations of dopamine and its metabolites in the hypothalamus 30 minutes after injection. GIZh-298 at a dose of 60 mg/kg caused an increase in the serotonin and dopamine concentration in the frontal cortex and a decrease in the dopamine metabolism rate in the dorsal striatum 30 minutes after injection, which may be considered as one of the components of the antiepileptic effect of this drug.

The purpose of this research was to study electric and physiological mechanisms of the achievement of the antoconvulsant effect of the new original beprodon combination together with determination of determinant brain structures – therapeutic targets.Materials and Methods. Partial (focal) and secondary generalized convulsions were generated using the method of creation of a chronic epileptogenic focus, caused by the cobalt application on rats’ brain.Results: it was revealed, that at the first stage of the epileptic system (ES) beprodone is targeted to cortical focuses, and at the second stage – to subcortical focuses, generating epileptic activities. Conclusion: the beprodone effect depends on the stage of the epileptic system development and is targeted to determinant focuses.

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.

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.

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.