ANTIDEPRESSANT-LIKE ACTIONS OF THE POLYAMINE SITE NMDA ANTAGONIST, ELIPRODIL (SL-82.0715)
ANTIDEPRESSANT-LIKE ACTIONS OF THE POLYAMINE SITE NMDA ANTAGONIST, ELIPRODIL (SL-82.0715)
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DOI：
10.1016/0091-3057(95)00155-p
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发表时间：
1995-11-01
影响因子：
3.6
通讯作者：
SKOLNICK, P
中科院分区：
文献类型：
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作者：
LAYER, RT;POPIK, P;SKOLNICK, P
功能性N-甲基-D-天冬氨酸（NMDA）拮抗剂包括竞争性拮抗剂、甘氨酸部分激动剂和使用依赖性通道阻滞剂，在临床前模型中表现出抗抑郁样作用。本研究考察了eliprodil（SL-82.0715），一种作用于多胺位点的NMDA拮抗剂，在行为和神经化学试验中预测抗抑郁活性的影响。在小鼠中，eliprodil在强迫游泳试验中产生了剂量依赖性的不动性降低，但在悬尾试验中无活性。eliprodil慢性治疗产生了β-肾上腺素受体的显著下调和甘氨酸抑制[H-3] 5，7-二氯犬尿烯酸与新皮质膜中士的宁不敏感甘氨酸受体结合的效力降低。总之，这些数据表明，与其他NMDA拮抗剂一样，eliprodil在预测临床疗效的临床前试验中具有抗抑郁样作用。
Functional N-methyl-D-aspartate (NMDA) antagonists including competitive antagonists, glycine partial agonists, and use-dependent channel blockers exhibit antidepressant-like actions in preclinical models. The present study examined the effects of eliprodil (SL-82.0715), an NMDA antagonist acting at polyamine sites, in behavioral and neurochemical tests predictive of antidepressant activity. In mice, eliprodil produced a dose-dependent reduction in immobility in the forced swim test, but was inactive in the tail suspension test. Chronic treatment with eliprodil produced both a significant downregulation of beta-adrenoceptors and a reduction in the potency of glycine to inhibit [H-3]5,7-dichlorokynurenic acid binding to strychnine-insensitive glycine receptors in neocortical membranes. In toto, these data indicate that like other NMDA antagonists, eliprodil possesses antidepressant-like actions in preclinical tests predictive of clinical efficacy.