The focused set of new pyrrolidine-2,5-diones as potential broad-spectrum hybrid anticonvulsants was described. These derivatives integrate on the common structural scaffold the chemical fragments of well-known antiepileptic drugs such as ethosuximide, levetiracetam, and lacosamide. Such hybrids demonstrated effectiveness in two of the most widely used animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure models. Compound 33 showed the highest anticonvulsant activity in these models (ED₅₀ MES = 79.5 mg/kg, ED₅₀ 6 Hz = 22.4 mg/kg). Compound 33 was also found to be effective in pentylenetetrazole-induced seizure model (ED₅₀ PTZ = 123.2 mg/kg). In addition, 33 demonstrated effectiveness by decreasing pain responses in formalin-induced tonic pain, in capsaicin-induced neurogenic pain, and notably in oxaliplatin-induced neuropathic pain in mice. The pharmacological data of stereoisomers of compound 33 revealed greater anticonvulsant activity by R(+)-33 enantiomer in both MES and 6 Hz seizure models.

中文翻译：

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具有抗惊厥和抗伤害特性的2-（2,5-二氧杂吡咯烷-1-基）-3-甲氧基丙酰胺衍生的多功能杂化化合物

描述了新的吡咯烷-2,5-二酮作为潜在的广谱杂化抗惊厥药的重点研究对象。这些衍生物在常见的结构支架上整合了著名的抗癫痫药物（如乙巯丁二酰亚胺，左乙拉西坦和拉考酰胺）的化学片段。这样的杂种在两个最广泛使用的动物癫痫发作模型中表现出有效性，即最大电击（MES）测试和精神运动性6 Hz（32 mA）癫痫发作模型。在这些模型中，化合物33显示出最高的抗惊厥活性（ED ₅₀ MES = 79.5 mg / kg，ED ₅₀ 6 Hz = 22.4 mg / kg）。还发现化合物33在戊四唑诱导的癫痫发作模型中有效（ED ₅₀ PTZ ＝ 123.2mg / kg）。此外，图33显示了通过减少福尔马林引起的强直性疼痛，辣椒素引起的神经性疼痛，特别是奥沙利铂引起的神经性疼痛的疼痛反应的有效性。化合物33的立体异构体的药理数据显示，在MES和6 Hz癫痫发作模型中，R（+）- 33对映异构体均具有更高的抗惊厥活性。