Gilbert Trevor H, Teskey G Campbell
Centre for Psychology, Athabasca University, 1 University Drive, T9S 3A3, Athabasca, AB, Canada.
Exp Brain Res. 2007 Mar;178(1):115-25. doi: 10.1007/s00221-006-0716-z. Epub 2007 Jan 26.
This study addressed the anticonvulsant effects of repeated administration of phenytoin, carbamazepine, phenobarbital, valproate, and ethosuximide in kindled guinea-pigs in order to further substantiate this novel model of partial seizures for the screening of future anticonvulsant drugs. Behavioral toxic effects were assessed at 30 min following drug administration using scores on a sedation/muscle relaxation rating index. In response to suprathreshold stimulation, the anticonvulsant efficacy of the drugs were evaluated from measurements of afterdischarge duration (ADD) and behavioral seizure severity (SS) during a repeated drug treatment schedule in kindled guinea-pigs. All drugs exerted slight to moderate sedative effects in guinea-pigs on our rating index. We found that phenytoin, carbamazepine, and phenobarbital exhibited effective anticonvulsant properties in kindled guinea-pigs by reducing both ADD and SS. We found that valproate consistently reduced ADD throughout the treatment schedule but failed to significantly reduce SS. Lastly, ethosuximide failed to exhibit effective anticonvulsant properties. Our results indicate that the guinea-pig kindling model correctly predicted the actions of these common anticonvulsant drugs in the treatment of partial seizures. Guinea-pig amygdala kindling appears to serve as a useful and valid model for partial epilepsy.
本研究探讨了苯妥英钠、卡马西平、苯巴比妥、丙戊酸盐和乙琥胺反复给药对点燃豚鼠的抗惊厥作用，以进一步证实这种新型部分性癫痫模型用于筛选未来抗惊厥药物的可行性。给药30分钟后，根据镇静/肌肉松弛评分指数评估行为毒性作用。在重复给药治疗方案期间，通过测量点燃豚鼠的放电后持续时间（ADD）和行为性癫痫严重程度（SS），评估药物对阈上刺激的抗惊厥效果。所有药物对豚鼠的评分指数均有轻微至中度的镇静作用。我们发现，苯妥英钠、卡马西平和苯巴比妥通过降低ADD和SS，在点燃豚鼠中表现出有效的抗惊厥特性。我们发现丙戊酸盐在整个治疗过程中持续降低ADD，但未能显著降低SS。最后，乙琥胺未表现出有效的抗惊厥特性。我们的结果表明，豚鼠点燃模型正确预测了这些常见抗惊厥药物在治疗部分性癫痫中的作用。豚鼠杏仁核点燃似乎是一种有用且有效的部分性癫痫模型。
