Abstract—The aim of this work was to study the involvement of the glutamate, dopamine, and serotonin receptors in the mechanism of the anticonvulsant action of the 4-benzoylpyridine oxime derivative (GIZH-298). After a single corneal exposure to the maximum electric shock (MES) and subsequent tonic–clonic seizures, an increase in the density (Bmax) of NMDA receptors in the hippocampus by 27% and a decrease in the number of mGluII receptors (mGluR2/ 3) by 25% in the prefrontal cortex of the brain of rats were noted. At the same time, the number of 5-HT2A receptors in the prefrontal cortex did not change. GIZH-298 (60 mg/kg) with a single application inhibits convulsive reactions but does not affect the quantitative changes induced by MES in glutamate receptors and does not affect them under normal conditions without MES. In tests on mice, subchronic (5 days) corneal exposure to MES reduced the density (Bmax) of D₂ receptors in the striatum by 17% and did not change this parameter in the prefrontal cortex. GIZH-298 (60 mg/kg/5 days) eliminates clonic–tonic convulsions in mice and prevents a decrease in the number of D₂ receptors from striatal membranes and also increases their number by 13% in mice without MES in the same structure. The data we obtained indicate significant changes in the functional activity of the NMDA, mGluII, and D₂ receptors in the brains of animals that suffered seizures. The anticonvulsant effects of GIZH-298 are accompanied by the restoration of the number of D₂ receptors in the striatum.

摘要- 这项工作的目的是研究谷氨酸、多巴胺和血清素受体在 4-苯甲酰吡啶肟衍生物 (GIZH-298) 的抗惊厥作用机制中的作用。在单次角膜暴露于最大电击 (MES) 和随后的强直阵挛发作后，海马体中 NMDA 受体的密度 (Bmax) 增加 27%，mGluII 受体 (mGluR2/ 3) 数量减少) 在大鼠大脑的前额叶皮层中增加了 25%。与此同时，前额叶皮层中的 5-HT2A 受体数量没有变化。GIZH-298 (60 mg/kg) 单次应用抑制惊厥反应，但不影响 MES 诱导的谷氨酸受体的数量变化，在没有 MES 的正常条件下也不影响它们。在小鼠实验中，₂纹状体中的受体增加了 17%，并且没有改变前额皮质中的这个参数。_{GIZH-298（60 mg/kg/5 天）消除小鼠的阵挛-强直性惊厥，防止纹状体膜 D 2}受体数量减少，并且在相同结构中没有 MES 的小鼠中它们的数量增加 13%。我们获得的数据表明，遭受癫痫发作的动物大脑中NMDA、mGluII 和 D _{2受体的功能活动发生了显着变化。}GIZH-298 的抗惊厥作用伴随着纹状体中D _{2受体数量的恢复。}