The neuroprotective effect of the forebrain-selective NMDA antagonist CP101,606 upon focal ischemic brain damage caused by acute subdural hematoma in the rat.
The neuroprotective effect of the forebrain-selective NMDA antagonist CP101,606 upon focal ischemic brain damage caused by acute subdural hematoma in the rat.
复制标题
前脑选择性 NMDA 拮抗剂 CP101,606 对大鼠急性硬膜下血肿引起的局灶性缺血性脑损伤的神经保护作用。
DOI：
10.1089/neu.1997.14.409
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Bullock,R
中科院分区：
文献类型：
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作者：
Tsuchida,E;Rice,M;Bullock,R
抗谷氨酸引起的兴奋性毒性损伤的药物的神经保护作用在局灶性缺血中得到了很好的描述，但行为效应，以及“第一代”竞争性N-甲基-天冬氨酸(NMDA)拮抗剂，如Selfotel(CGS19755)的临床试验明显失败，使人们有兴趣评估行为影响较小的新的NMDA拮抗剂。因此，我们评估了一种新的前脑选择性多胺位点NMDA拮抗剂CP101,606在大鼠硬膜下血肿(SDH)模型中的神经保护作用。自体血0.4ml缓慢注入顶膜硬膜下腔形成SDH。在血肿诱导4h后处死动物，在8个冠状平面上对脑损伤进行组织学评估。CP101、606对脑缺血损伤的保护作用，低剂量组为29%，高剂量组为37%。在同一模型中，这种新型谷氨酸拮抗剂的神经保护作用与“第一代”NMDA拮抗剂如MK801、D-CPP-ene和CGS19755相当。这种新的药物声称比MK801，D-CPP-ene和CGS19755有更少的精神运动和行为影响。
The neuroprotective effects of drugs that act against excitotoxic damage, caused by glutamate, are well described in focal ischemia, but behavioral effects, and apparent failure in clinical trials of "first-generation" competitiveN-methyld-aspartate (NMDA) antagonists, such as Selfotel (CGS19755), has led to interest in evaluating newer NMDA antagonists with fewer behavioral effects. We have therefore evaluated the neuroprotective effect of a new forebrain-selective polyamine site NMDA antagonist, CP101,606 in a rat subdural hematoma (SDH) model. An SDH was produced by slow injection of 0.4 ml autologous blood into the parietal subdural space. Brain damage was assessed histologically at eight coronal planes, in animals sacrificed 4 h after induction of hematoma. The drug was infused 30 min after induction of SDH.The reductions of ischemic brain damage achieved by CP101,606, was 29% for the low dose and 37% for the high dose. This novel glutamate antagonist has shown a magnitude of neuroprotection which is comparable with that seen with "first-generation" NMDA antagonists such as MK801, D-CPP-ene and CGS19755, in this same model. This new agent is claimed to have fewer psychomotor and behavioral effects than MK801, D-CPP-ene, and CGS19755.