Long-lasting antiepileptic effects of levetiracetam against epileptic seizures in the spontaneously epileptic rat (SER): Differentiation of levetiracetam from conventional antiepileptic drugs
Long-lasting antiepileptic effects of levetiracetam against epileptic seizures in the spontaneously epileptic rat (SER): Differentiation of levetiracetam from conventional antiepileptic drugs
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DOI：
10.1111/j.1528-1167.2005.29604.x
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发表时间：
2005-09-01
期刊：
影响因子：
5.6
通讯作者：
Sasa, M
中科院分区：
文献类型：
--
作者：
Ji-qun, C;Ishihara, K;Sasa, M
目的：有证据表明左乙拉西坦（LEV）具有抗癫痫作用。本研究旨在探讨LEV与苯妥英（PHT）、苯巴比妥（PB）、丙戊酸（VPA）、卡马西平（CBZ）对自发性癫痫大鼠（SER）的癫痫发作保护作用的时间过程。SER为双突变体（tm/tm, zi/zi），表现为强直性惊厥和失神样癫痫发作。方法：观察单次（40、80、160 mg/kg, i.p）和5天（80 mg/kg/d, i.p）给药LEV对强直性惊厥和缺席样癫痫发作的影响。以5分钟为间隔，连续30分钟向动物头部吹气引起强直性惊厥，并记录自发性失神样癫痫发作30分钟，其特征是皮层和海马脑电图中出现5至7赫兹的尖波样复合体。在单次给药研究中，分别在给药前1次和给药后3次（45、75和135分钟）观察癫痫发作活动。5天给药研究中，5天给药期间癫痫发作观察4次，每次30 min（给药前1次，给药后3次），每天1次，直至给药后8天。常规抗癫痫药（PHT、PB、VPA、CBZ）给药5 d后的抗癫痫效果采用相同方法观察。结果：单次给药80、160 mg/kg （i.p）可抑制强直性惊厥和缺席样癫痫发作，但在40 mg/kg （i.p）时不显著。连续5天以80 mg/kg/d （i.p）给药至SERs，对癫痫发作的抑制作用随给药时间增加而增强。在给药5 d后，强直性惊厥和缺席样癫痫的发生率分别显著降低至39.1%和38.4%。此外，还发现强直性惊厥有明显的抑制作用
Purpose: Some evidence suggests that levetiracetam (LEV) possesses antiepileptogenic characteristics. The purpose of this study was to investigate the time course of seizure protection by LEV compared with that of phenytoin (PHT), phenobarbital (PB), valproate (VPA), and carbamazepine (CBZ) in the spontaneously epileptic rat (SER). The SER is a double mutant (tm/tm, zi/zi) showing both tonic convulsions and absence-like seizures.Methods: The effect of single (40, 80, and 160 mg/kg, i.p.) and 5-day (80 mg/kg/day, i.p.) administration of LEV on tonic convulsions and absence-like seizures in SERs were studied. Tonic convulsions induced by blowing air onto the animal's head at 5-min intervals for 30 min and spontaneous absence-like seizures characterized by 5- to 7-Hz spike-wave-like complexes in the cortical and hippocampal EEG were recorded for 30 min. In the single-administration study, observations for seizure activity were performed once before and 3 times (45, 75, and 135 min) after drug administration. In the 5-day administration study, seizure observation was performed 4 times for 30 min (once before and 3 times after drug administration) during the 5-day drug-administration period, and continued once a day until 8 days after the final administration. The antiepileptic effects of 5-day administration of conventional AEDs (PHT, PB, VPA, and CBZ) were examined by using similar methods.Results: Tonic convulsions and absence-like seizures were inhibited by a single administration of LEV at 80 and 160 mg/kg, i.p., but not significantly at 40 mg/kg, i.p. When LEV was repeatedly administered at 80 mg/kg/day, i.p., for 5 days to SERs, the inhibitory effects on seizures increased with administration time. The number of tonic convulsions and absence-like seizures were significantly reduced to 39.1% and 38.4% compared with previous values, respectively, after 5-day LEV administration. Furthermore, significant inhibition of tonic convulsions was detected