Establishment of evaluation of long-term effects of antiepileptic drugs in the spontaneously epileptic rat

抗癫痫药物对自发性癫痫大鼠远期疗效评价的建立

基本信息

批准号：
02557102
负责人：
SASA Masashi
金额：
$ 4.42万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

The spontaneously epileptic rat (SER) is a double mutant (zi/zi, te/tm) that exhibits both tonic convulsion and absence-like seizure. Sodium valproate (VPA) is known to be effective in the treatment of primary generalized seizures and absence-like seizures in humans. Our previous study demonstrates that an acute administration of VPA suppresses both tonic and absence-like seizures in SER. The study was performed to determine whether or not this animal is useful in evaluation of clinical characteristics of antiepileptics when the drugs were orally given for long-term period. Chronic treatment with VPA using food pellets containing either 1 or 5 % VPA from 7 weeks of age significantly prolonged the survival time of SER compared to the control. The plasma concentrations of VPA after 10-week treatment were 17.3 and 82.5 mug/ml in the 1 and 5 % VPA groups, respectively. Tonic convulsion fully developed at 14 weeks of age in the control group (8.3 times/2 hours). At the same age, the tonic convulsion in l % (5.1 times/2 hours) and 5 % (2.1 times/2 hours) VPA groups were significantly suppressed compared to the control group. In addition, absence-like seizures characterized by sudden appearance of 5-7 Hz spike and wave complex were also inhibited in 1 VPA group. There were no tolerance development to the inhibitory effects of the drugs. These results are in accordance with those seen in epileptic patients. Furthermore, there were no abnormal findings on liver function of 1 % VPA group except for slight elevation of GOT and GPT in 5 % VPA group. Thus, these results suggest that SER is useful in the evaluation of clinical profiles of antidpileptic drugs for longterm period.

自发性癫痫大鼠（SER）是一种双突变体（Zi/Zi，TE/TM），表现出滋补性抽搐和缺乏性癫痫发作。已知丙戊酸钠（VPA）可有效治疗人类的原发性癫痫发作和缺失癫痫发作。我们先前的研究表明，VPA的急性施用抑制了Ser中的滋补和缺失样的癫痫发作。进行该研究是为了确定该动物长期服用药物时是否有助于评估抗癫痫剂的临床特征。与对照组相比，使用含有1或5％VPA的食品颗粒对VPA进行慢性处理，从而显着延长了SER的生存时间。 10周治疗后VPA的血浆浓度分别为17.3和82.5 mug/ml，分别为1和5％VPA组。在对照组的14周龄（8.3次/2小时）时，滋补抽搐在14周龄中充分发育。在同一年龄，与对照组相比，在L％（5.1次/2小时）和5％（2.1次/2小时）的5％（2.1次/2小时）的补体抽搐被显着抑制。此外，在1 VPA组中，还抑制了以5-7 Hz尖峰和波复合物突然出现的特征的缺失样癫痫发作。对药物的抑制作用没有耐受性的发展。这些结果与癫痫患者中看到的结果一致。此外，除了5％VPA组的GOT和GPT略微升高外，对1％VPA组的肝功能没有异常的发现。因此，这些结果表明SER可用于评估长期抗毒药物的临床特征。