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比较抗惊厥疗效在部分癫痫角膜点燃鼠模型:与其他癫痫发作和癫痫模型的相关性。

Comparative anticonvulsant efficacy in the corneal kindled mouse model of partial epilepsy: Correlation with other seizure and epilepsy models.

机构信息

Anticonvulsant Drug Development Program, Department of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT 84108, USA.

出版信息

Epilepsy Res. 2010 Dec;92(2-3):163-9. doi: 10.1016/j.eplepsyres.2010.09.002. Epub 2010 Oct 14.

Abstract

Chronic electrical stimulation via corneal electrodes can rapidly yield large numbers of kindled mice with a seizure phenotype reflective of secondarily generalized partial seizures. The corneal kindled mouse model has been found to be a highly sensitive and efficient screening model for antiepileptic drug (AED) discovery. The present study further evaluates the utility of the corneal kindled mouse model as a tool for rapid screening of investigational AEDs. Results obtained with nine AEDs (valproic acid, lamotrigine, phenytoin, carbamazepine, levetiracetam, vigabatrin, topiramate, tiagabine, and ezogabine) with varying mechanisms of action and clinical spectrums, as well as six investigational compounds were evaluated in the corneal kindled mouse. ED(50) values are compared to those obtained in the hippocampal kindled rat, the mouse maximal electroshock (MES) model, the 6Hz partial psychomotor seizure model, and the subcutaneous pentylenetetrazol (scPTZ) test. The results obtained in the corneal kindled mouse demonstrate a positive correlation with those attained employing established preclinical models: MES (r² = 0.9511), scPTZ (r² = 0.9697), 6Hz (r² = 0.9519), and hippocampal kindling (r² = 0.9037). The demonstrated predictive ability of the corneal kindled mouse model supports its use in the early evaluation of investigational AEDs.

摘要

通过角膜电极进行慢性电刺激可以快速产生大量具有继发性全身性部分发作特征的点燃小鼠。已经发现角膜点燃小鼠模型是一种高度敏感和有效的抗癫痫药物(AED)发现筛选模型。本研究进一步评估了角膜点燃小鼠模型作为快速筛选研究性 AED 的工具的效用。评估了具有不同作用机制和临床谱的九种 AED(丙戊酸、拉莫三嗪、苯妥英、卡马西平、左乙拉西坦、加巴喷丁、托吡酯、噻加宾和依佐加滨)以及六种研究性化合物在角膜点燃小鼠中的作用。ED(50)值与在海马点燃大鼠、小鼠最大电休克(MES)模型、6Hz 部分精神运动性癫痫发作模型和皮下戊四氮(scPTZ)测试中获得的值进行比较。在角膜点燃小鼠中获得的结果与使用既定临床前模型获得的结果呈正相关:MES(r² = 0.9511)、scPTZ(r² = 0.9697)、6Hz(r² = 0.9519)和海马点燃(r² = 0.9037)。角膜点燃小鼠模型的预测能力表明其可用于研究性 AED 的早期评估。

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