甘氨酮抑制小鼠杏仁核点燃模型的行为和脑电图发作。
Ganaxolone suppression of behavioral and electrographic seizures in the mouse amygdala kindling model.
机构信息
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M System Health Science Center, College Station, TX 77843-1114, USA.
出版信息
Epilepsy Res. 2010 May;89(2-3):254-60. doi: 10.1016/j.eplepsyres.2010.01.009. Epub 2010 Feb 20.
Abstract
Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive allosteric modulator of GABAA 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.
摘要
ganaxolone（3α-羟基-3β-甲基-5α-孕烷-20-酮）是内源性神经甾体 allopregnanolone 的合成类似物，也是 GABAA 受体的正变构调节剂，可能代表了治疗癫痫的新方法。在这里，我们证明 ganaxolone（1.25-20mg/kg，sc）预处理可导致完全杏仁核点燃的雌性小鼠的行为和脑电图发作呈剂量依赖性抑制，在测试的最高剂量下几乎完全保护癫痫发作。抑制行为性发作的 ED50 为 6.6mg/kg。ganaxolone 产生的癫痫抑制作用与氯硝西泮（ED50，0.1mg/kg，sc）相当。在杏仁核点燃代表内侧颞叶癫痫模型的程度上，这项研究支持 ganaxolone 在治疗颞叶发作患者中的效用。
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