Armand V, Louvel J, Pumain R, Ronco G, Villa P
Inserm U 7, Paris, France.
Epilepsy Res. 1995 Nov;22(3):185-92. doi: 10.1016/0920-1211(95)00044-5.
Lowering of extracellular calcium induces the development of spontaneous epileptiform activities in rat hippocampal slices. The antiepileptogenic effect of four new sugar-ester derivatives of valproic acid--dimethylenexylitol valproate, monoacetoneglucose valproate, diacetoneglucose valproate and glucose valproate--were investigated on such activity through 20-min bath applications and their effect compared to that of valproate, valpromide and phenytoin. Sodium valproate, 5 mM, did not completely suppress the spontaneous epileptiform activity. Valpromide, 2.5 mM, and phenytoin, 0.25 mM, produced complete cessation of seizure activity. Dimethylenexylitol valproate, 0.1 mM, completely suppressed spontaneous epileptiform activities. The other derivatives were less potent: concentrations of 0.25 mM of monoacetoneglucose valproate and 1 mM of diacetoneglucose valproate and glucose valproate were required for complete cessation of activity. The sugar carriers alone were devoid of effect. The data show that these molecules have a direct action on the nervous tissue and their antiepileptogenic efficacy in the low-calcium model is far larger than that of valproic acid itself. Such derivatives, especially dimethylenexylitol valproate, appear to be promising for development of new antiepileptic molecules.
降低细胞外钙会诱导大鼠海马切片中出现自发性癫痫样活动。通过20分钟的浴槽给药，研究了四种新型丙戊酸糖酯衍生物——丙戊酸二亚甲基木糖醇酯、丙戊酸单丙酮葡萄糖酯、丙戊酸二丙酮葡萄糖酯和丙戊酸葡萄糖酯——对这种活动的抗癫痫作用，并将它们的效果与丙戊酸盐、丙戊酰胺和苯妥英钠进行比较。5 mM的丙戊酸钠不能完全抑制自发性癫痫样活动。2.5 mM的丙戊酰胺和0.25 mM的苯妥英钠可使癫痫活动完全停止。0.1 mM的丙戊酸二亚甲基木糖醇酯可完全抑制自发性癫痫样活动。其他衍生物的效力较低：完全停止活动需要0.25 mM的丙戊酸单丙酮葡萄糖酯、1 mM的丙戊酸二丙酮葡萄糖酯和丙戊酸葡萄糖酯。仅糖载体没有作用。数据表明，这些分子对神经组织有直接作用，并且它们在低钙模型中的抗癫痫疗效远大于丙戊酸本身。这类衍生物，尤其是丙戊酸二亚甲基木糖醇酯，似乎有望用于开发新的抗癫痫分子。
