Ganaxolone suppression of behavioral and electrographic seizures in the mouse amygdala kindling model
Ganaxolone suppression of behavioral and electrographic seizures in the mouse amygdala kindling model
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DOI：
10.1016/j.eplepsyres.2010.01.009
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发表时间：
2010-05-01
影响因子：
2.2
通讯作者：
Rogawski, Michael A.
中科院分区：
文献类型：
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作者：
Reddy, Doodipala S.;Rogawski, Michael A.
加奈索酮（3 α-羟基-3 β-甲基-5 α-葡聚糖-20-酮）是内源性神经甾体别孕烯醇酮的合成类似物，也是GABA（A）受体的正变构调节剂，可能代表癫痫的新治疗方法。在此，我们证明用加奈索酮（1.25-20 mg/kg，s.c.）在杏仁核完全点燃的雌性小鼠中，对行为和电图癫痫发作产生剂量依赖性抑制，在最高试验剂量下几乎完全保护癫痫发作。抑制行为性癫痫发作的ED 50为6.6 mg/kg。加奈索酮产生的癫痫发作抑制与氯硝西泮相当（ED 50，0.1 mg/kg，皮下注射）。在杏仁核点燃代表内侧颞叶癫痫模型的程度上，本研究支持加奈索酮治疗颞叶癫痫患者的效用。(C)2010 Elsevier B. V.保留所有权利。
Ganaxolone (3 alpha-hydroxy-3 beta-methyl-5 alpha-pregnan-20-one), a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive allosteric modulator of GABA(A) receptors, may represent a new treatment approach for epilepsy. Here we demonstrate that pretreatment with ganaxolone (1.25-20 mg/kg, s.c.) causes a dose-dependent suppression of behavioral and electrographic seizures in fully amygdala-kindled female mice, with nearly complete seizure protection at the highest dose tested. The ED50 for suppression of behavioral seizures was 6.6 mg/kg. The seizure suppression produced by ganaxolone was comparable to that of clonazepam (ED50, 0.1 mg/kg, s.c.). To the extent that amygdala kindling represents a model of mesial temporal lobe epilepsy, this study supports the utility of ganaxolone in the treatment of patients with temporal lobe seizures. (C) 2010 Elsevier B.V. All rights reserved.