Armand V, Louvel J, Pumain R, Heinemann U
Department of Neurophysiology, Insitute of Physiology of the Charité, Humboldt University Berlin, Germany.
Epilepsy Res. 1998 Nov;32(3):345-55. doi: 10.1016/s0920-1211(98)00030-8.
The effects of four valproic acid derivatives were studied on pentylenetetrazole-induced epileptiform discharges in combined entorhinal cortex hippocampus slices. The two new sugar-esters of valproic acid, dimethylenexylitol valproate (VDMX, 0.5 mM) and glucose valproate (VG, 2 mM) abolished the epileptiform activity. These two new derivatives were compared to two clinically used anticonvulsant drugs, valpromide (2 mM) which suppressed the activity and valproic acid (2 mM), which was ineffective. The new drugs VDMX and VG were also tested on different patterns of epileptiform activity induced by lowering of [Mg2+]0. A 1 mM concentration of VDMX and 2 mM VG, reversibly suppressed the recurrent short discharges in area CA1 and the seizure-like events in the entorhinal cortex. A concentration of 2 mM VDMX was required to abolish the late recurrent discharges in entorhinal cortex. VG at 2 mM reduced the frequency of these discharges by 58.5+/-9.5%.
研究了四种丙戊酸衍生物对戊四氮诱导的内嗅皮质-海马联合切片中癫痫样放电的影响。两种新的丙戊酸糖酯，亚甲基木糖醇丙戊酸酯（VDMX，0.5 mM）和葡萄糖丙戊酸酯（VG，2 mM）消除了癫痫样活动。将这两种新衍生物与两种临床使用的抗惊厥药物进行比较，即抑制活性的丙戊酰胺（2 mM）和无效的丙戊酸（2 mM）。还对通过降低[Mg2+]0诱导的不同模式的癫痫样活动测试了新药VDMX和VG。1 mM浓度的VDMX和2 mM的VG可逆地抑制了CA1区的反复短放电和内嗅皮质中的癫痫样事件。需要2 mM的VDMX浓度来消除内嗅皮质中的晚期反复放电。2 mM的VG使这些放电的频率降低了58.5±9.5%。
