PDF(Pubmed)
Abstract：
Stiripentol (STP, Diacomit©) is an antiseizure medication indicated for Dravet syndrome, a rare developmental and epileptic encephalopathy characterized by drug-resistant seizures, including status epilepticus (SE). SE is a life-threatening event that may lead to increased risk of morbidity and mortality. Here, we evaluated the effect of STP on SE and SE-associated mortality using a CBA mouse model induced by systemic administration of methionine sulfoximine (MSO), an irreversible inhibitor of glutamine synthetase. MSO induces convulsions, prolonged seizure (SE) and death, with an increase of blood ammonia level. A single acute intraperitoneal pretreatment with 200-300-400 mg/kg of STP significantly inhibited the number of seizures, SE occurrence and death in MSO-treated animals in a dose-dependent manner. Regarding blood ammonia level, STP significantly reduced by 41 % the hyperammonemia induced by MSO. In conclusion, our results show protective effects of STP to reduce and or suppress the occurrence of SE as well as its associated mortality in mice.
摘要：
Stiripentol(STP,Diacomit©)是一种用于Dravet综合征的抗癫痫药物，一种罕见的以抗药性癫痫发作为特征的发育性和癫痫性脑病，包括癫痫持续状态（SE）。SE是一种危及生命的事件，可能导致发病率和死亡率增加。这里,我们使用全身给药蛋氨酸亚砜胺（MSO）诱导的CBA小鼠模型评估了STP对SE和SE相关死亡率的影响，一种不可逆的谷氨酰胺合成酶抑制剂.MSO诱发抽搐,长时间癫痫发作（SE）和死亡，随着血氨水平的增加。单次急性腹腔内预处理200-300-400mg/kgSTP显著抑制癫痫发作次数,MSO处理的动物中SE的发生和死亡呈剂量依赖性。关于血氨水平，STP可显著降低MSO引起的高氨血症41%。总之,我们的结果显示STP在小鼠中具有降低和/或抑制SE的发生及其相关死亡率的保护作用.
