托吡酯对大鼠杏仁核点燃的抑制作用  

Inhibition of topiramate on amygdala kindling in rats

作　　者：周明[1] 刘艳霞[1] 杨志宏[1] 郭沈波[1] 邵伯芹[1] 岳旺[1] 

机构地区：[1]青岛大学医学院药理学教研室,青岛266021

出　　处：《中国药理学通报》2002年第1期58-60,共3页Chinese Pharmacological Bulletin

基　　金：国家教育部资助课题 ;No 1995 80 6

摘　　要：目的　在大鼠杏仁核点燃模型研究抗癫痫新药托吡酯的抗癫痫作用及其作用机制。方法　建立大鼠杏仁核电刺激点燃模型 ,并通过联合用药探讨托吡酯对点燃的作用及其可能机制 ;测定托吡酯对小鼠氨基脲惊厥的影响。结果　托吡酯 (5 0～ 2 0 0mg·kg-1,ig)可剂量依赖性抑制杏仁核点燃 (P <0 0 5 )。在对点燃均无明显影响的低剂量下 ,托吡酯与丙戊酸钠或尼卡地平合用可缩短后放电时程 (P <0 0 5 )。托吡酯 2 0 0mg·kg-1,ig ,降低小鼠氨基脲诱发的惊厥发生率和死亡率 (P <0 0 1)。结论　托吡酯能抑制杏仁核点燃 ,与丙戊酸钠、尼卡地平有协同效应 ,其机制可能与GABA能神经功能增强以及Ca2 + 拮抗有关。AIM To investigate the role and mechanism of a novel antiepileptic drug topiramate on amygdala kindling in rats. METHODS The effects and mechanism of topiramate on kindling were examined by the establishment of amygdala kindling model and combination with other drugs. The influence of topiramate on seizures induced by semicarbazide hydrochloride(SCZ) was also observed. RESULTS Topiramate (50～200 mg·kg -1 ,ig) dose-dependently inhibited the seizure severity in amygdala kindling ( P< 0.05). The combination of topiramate with valproate sodium or nicardipine, all in ineffective doses on kindling, decreased ADD( P< 0.05). Topiramate 200 mg·kg -1 ,ig decreased the rate of seizure and death induced by SCZ in mice( P< 0.01). CONCLUSION Topiramate can significantly inhibit amygdala kindling in rats, and has synergism with valproate sodium and nicardipine, with the possible mechanism of GABA-ergic inhibition as well as Ca 2+ -channel blockade.

关 键 词：托吡酯 杏仁核点燃 丙戊酸钠 尼卡地平 癫痫 实验研究 

分 类 号：R971.6[医药卫生—药品] R742.1[医药卫生—药学]