Morimoto K, Sato H, Yamamoto Y, Watanabe T, Suwaki H
Department of Neuropsychiatry, Faculty of Medicine, Kagawa Medical University, Japan.
Epilepsia. 1997 Sep;38(9):966-74. doi: 10.1111/j.1528-1157.1997.tb01478.x.
We determined the antiepileptic profile of tiagabine (TGB), a selective gamma-aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of temporal lobe epilepsy (TLE).
The anticonvulsant and adverse effects of TGB were examined in amygdala- or hippocampal-kindled rats and compared with those of other GABA uptake inhibitors (SKF89976A and NNC-711) and conventional antiepileptic drugs [AEDs: valproate (VPA) and carbamazepine (CBZ)]. In addition, the antiepileptogenic effects of TGB on amygdala kindling development were examined.
TGB (2.5-40 mg/kg intraperitoneally, i.p.) had potent and dose-dependent anticonvulsant effects on both amygdala- and hippocampal-kindled seizures. The order of anticonvulsant potency of the three GABA uptake inhibitors tested was: NNC-711 > TGB > SKF-89976A and paralleled the in vitro GABA uptake efficacy. In addition, daily treatment with TGB 10 mg/kg for 10 days significantly retarded kindling development. Although adverse effects of TGB on motor systems were significantly less than those of VPA and CBZ, high toxic doses of TGB often caused EEG paroxysm and myoclonus.
Our results indicate the clinical usefulness of TGB for treatment of drug-resistant TLE.
我们在颞叶癫痫（TLE）的大鼠点燃模型中确定了选择性γ-氨基丁酸（GABA）摄取抑制剂替加宾（TGB）的抗癫痫谱。
在杏仁核或海马点燃的大鼠中检测TGB的抗惊厥和不良反应，并与其他GABA摄取抑制剂（SKF89976A和NNC-711）及传统抗癫痫药物[AEDs：丙戊酸盐（VPA）和卡马西平（CBZ）]进行比较。此外，还检测了TGB对杏仁核点燃发展的抗癫痫发生作用。
TGB（腹腔注射2.5 - 40mg/kg）对杏仁核和海马点燃的癫痫发作均有强效且剂量依赖性的抗惊厥作用。所测试的三种GABA摄取抑制剂的抗惊厥效力顺序为：NNC-711 > TGB > SKF-89976A，且与体外GABA摄取效力平行。此外，每天用10mg/kg的TGB治疗10天可显著延缓点燃发展。尽管TGB对运动系统的不良反应明显少于VPA和CBZ，但高毒剂量的TGB常引起脑电图发作和肌阵挛。
我们的结果表明TGB在治疗耐药性TLE方面具有临床实用性。
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