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.

中文翻译：

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肟肟吡啶衍生物（GIZh-298）对最大电击诱发癫痫发作大鼠脑中单胺及其代谢产物含量的影响

摘要-我们研究了可能的抗癫痫药GIZh-298和比较药物托吡酯对全身性强直性强直性兴奋剂对大鼠大脑额叶皮质，下丘脑，伏隔核，纹状体和海马中单胺及其代谢物浓度的影响。电击（MES）引起的阵挛性癫痫发作。我们发现GIZh-298（60 mg / kg，ip）在MES拮抗试验中显示出明显的抗惊厥作用，并防止多巴胺能系统功能活性的增加和相同结构中去甲肾上腺素（NE）含量的减少。托吡酯（100 mg / kg，ip）以及GIZh-298，阻止了MES引起的癫痫发作的发生，并刺激纹状体中的NA水平升高至正常值，但并未影响MES引起的黑质纹状体多巴胺能系统功能活性的变化。因此，可以得出结论，纹状体中去甲肾上腺素能神经传递的调节是GIZh-298和托吡酯在MES拮抗试验中抗惊厥作用的机制之一，此外，GIZh-298与托吡酯不同，响应于MES，有助于减少该结构中多巴胺能系统的功能活性。