Influence of lamotrigine and topiramate on MDR1 expression in difficult-to-treat temporal lobe epilepsy
Influence of lamotrigine and topiramate on MDR1 expression in difficult-to-treat temporal lobe epilepsy
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DOI：
10.1111/j.1528-1167.2006.00414.x
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发表时间：
2006-02-01
期刊：
影响因子：
5.6
通讯作者：
Stefan, H
中科院分区：
文献类型：
--
作者：
Wang-Tilz, Y;Tilz, C;Stefan, H
目的：定量测定了拉莫三嗪（LTG）或托吡酯（TPM）治疗后马桑内酯（CL）点燃的Sprague-Dawley（SD）大鼠脑组织中多药耐药基因1（MDR 1）的过表达，并与卡马西平（CBZ）和丙戊酸盐（VPA）治疗的大鼠进行比较。方法：25只CL点燃SD大鼠随机分为5组（每组n = 5）接受CBZ、VPA、TPM和LTG每日一次喂养，作为最大成人剂量的单药治疗等效物，或生理盐水（NS对照）处理1个月。采用图像分析和测量系统（ImagePro-plus 4.0）定量所有大鼠脑组织中P-gp的表达。计算P-gp表达的平均面积和平均积分光密度（平均IOD）。此外，癫痫发作的严重程度的变化进行了分析，通过摄像头monitoring.Results：一个显着减少癫痫发作的数量和持续时间与抗癫痫药物（AED）治疗观察TPM和LTG组。P-gp表达的平均面积和平均IOD在CBZ组最高，VPA组次之，TPM和LTG组较低，NS对照组最低（p < 0.05）。TPM和LTG对P-gp表达无明显影响。
Purpose: Overexpression of the multiple drug resistance gene 1 (MDR1) was quantified in brain tissue from Coriaria lactone (CL)-kindled Sprague-Dawley (SD) rats after treatment with lamotrigine (LTG) or topiramate (TPM) and compared with that found in rats treated with carbamazepine (CBZ) and valproate (VPA).Methods: Twenty-five CL-kindled SD rats were randomized into five groups (n = 5 for each group) to receive once-daily feeding of CBZ, VPA, TPM, and LTG as the monotherapy equivalent of maximum human adult dosage, or normal saline (NS control) for 1 month. The expression of P-gp in brain tissues of all rats was quantified by using an image analysis and measuring system (Image Pro-plus 4.0). Mean area and mean integrated optical density (mean IOD) of P-gp expression were calculated. In addition, the changes in seizure severity were analyzed via video-camera monitoring.Results: A significant decrease in the number and duration of seizures with antiepileptic drug (AED) treatment was observed in the TPM and LTG groups. The mean area and mean IOD of P-gp expression were highest in the CBZ group and next highest in the VPA group; much lower values were measured in the TPM and LTG groups, and the lowest in the NS control group (p < 0.05).Conclusions: TPM and LTG significantly inhibited seizures in this CL model. The expression of P-gp was not significantly increased by TPM or LTG treatment in this study.