NMDA RECEPTOR ANTAGONISTS AND LIMBIC STATUS EPILEPTICUS - A COMPARISON WITH STANDARD ANTICONVULSANTS
NMDA RECEPTOR ANTAGONISTS AND LIMBIC STATUS EPILEPTICUS - A COMPARISON WITH STANDARD ANTICONVULSANTS
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DOI：
10.1016/0920-1211(90)90036-u
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发表时间：
1990-04-01
影响因子：
2.2
通讯作者：
LOTHMAN, EW
中科院分区：
文献类型：
--
作者：
BERTRAM, EH;LOTHMAN, EW
癫痫持续状态（SE）在未经治疗的情况下会经历几个阶段。SE的后期阶段对标准抗惊厥药的反应较低，可能需要全身麻醉来抑制癫痫发作。作用于谷氨酸（兴奋性）受体的N-甲基-D-天冬氨酸（NMDA）亚类的拮抗剂已证明在某些癫痫发作模型中发挥抗癫痫活性。我们报告的实验，以确定是否NMDA受体拮抗剂是有效的，在停止癫痫发作的后期阶段的SE。采用连续电刺激大鼠海马90 min诱发边缘系统SE模型。比较了三种NMDA受体拮抗剂，一种“竞争性"（CPP）和两种”非竞争性“（氯胺酮和MK-801）与3种标准抗癫痫药物（地西泮、苯巴比妥和苯妥英）在生理学定义的SE阶段抑制癫痫发作的能力。所有NMDA受体拮抗剂，地西泮和苯巴比妥有效抑制行为和电图癫痫发作不同的时间。苯妥英钠对SE无影响。氯胺酮和MK-801诱导了SE抑制之前的电图癫痫发作的矛盾增强。我们认为，NMDA受体拮抗剂提供了一种新的方法来治疗SE的晚期阶段。
Status epilepticus (SE) evolves through several stages when untreated. The later stages of SE are less responsive to standard anticonvulsants and may require general anesthesia to suppress seizures. Antagonists acting at the N-methyl-D-aspartate (NMDA) subclass of glutamate (excitatory) receptors have demonstrated to exert antiepileptic activity in some seizure models. We report experiments performed to determine if NMDA receptors antagonists are effective in stopping seizures in the late stages of SE. A model of limbic SE induced by 90 min of ''continuous'' electrical stimulation of the hippocampus in rats was employed. Three NMDA receptor antagonists, one ''competitive'' (CPP) and two ''non-competitive'' (ketamine and MK-801), were compared to 3 standard antiepileptic drugs (diazepam, phenobarbital, and phenytoin) for their ability to suppress seizures at a physiologically defined stage of SE. All NMDA receptor antagonists, diazepam and phenobarbital were effective in suppressing behavioral and electrographic seizures for varying periods of time. Phenytoin had no effect on SE. Ketamine and MK-801 induced a paradoxical enhancement of electrographic seizures that preceded SE suppression. We believe that NMDA-receptor antagonists offer a novel approach for treating the late stages of SE.