Neuroprotectant effects of LY 274614, a structurally novel systemically active competitive NMDA receptor antagonist
Neuroprotectant effects of LY 274614, a structurally novel systemically active competitive NMDA receptor antagonist
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LY 274614 的神经保护作用，一种结构新颖的系统活性竞争性 NMDA 受体拮抗剂
DOI：
10.1007/bf01244705
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Leander Jd
中科院分区：
文献类型：
--
作者：
D. Schoepp;P. L. Ornstein;C. Salhoff;Leander Jd
N-甲基-D-天冬氨酸(NMDA)亚型谷氨酸受体拮抗剂可能在包括脑缺血、亨廷顿舞蹈病和阿尔茨海默病在内的神经元变性条件下作为神经保护剂具有治疗潜力。在这里，我们研究了结构新颖的竞争性N-甲基-D-天冬氨酸受体拮抗剂LY 274614的药理作用，包括全身给药后的药理选择性和神经保护作用。在10,000 nM范围内，LY-274614对[~3H]-cGS19755受体的结合无明显的亲和力(IC_(50)=58.8±10.3 nM)。对NMDA诱导的新生大鼠惊厥或NMDA诱导的小鼠致死性惊厥有明显的拮抗作用。或者是邮政总局。LY 274614。口服剂量显示出延迟但延长的效果持续时间。在成年大鼠中，纹状体内注射N-甲基-D-天冬氨酸或喹啉酸(而不是红藻氨酸)所致的神经退行性改变(胆碱乙酰转移酶活性丧失)可被LY 274614(2.520 mg/kg.ip)阻止。当全身给药时，LY 274614是一种有效的神经保护剂，可对抗N-甲基-D-天冬氨酸受体诱导的毒性，并且对于谷氨酸在神经元变性的病理过程中起作用的情况是一种有前途的治疗药物。
Antagonists for the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor may have therapeutic potential as neuroprotectant agents in conditions of neuronal degeneration that include brain ischemia, Huntington's chorea, and Alzheimer's disease. Here we have investigated the pharmacological actions of LY 274614, a structurally novel competitive NMDA receptor antagonist, for pharmacological selectivity and neuroprotectant effects following systemic administration. LY 274614 potently displaced NMDA receptor ([3H]CGS19755) binding (IC50=58.8±10.3 nM), but had no appreciable affinity at [3H]AMPA or [3H]kainate receptor sites at up to 10,000 nM. NMDA-induced convulsions in neonatal rats or NMDA-induced lethality in mice are potently and selectively antagonized by i.p. or p.o. LY 274614. Oral doses showed a delayed but prolonged duration of effect. In adult rats, the neuro-degenerative effects (loss of choline acetyltransferase activity) following the intrastriatal infusions of NMDA or quinolinate, but not kainate, were prevented by LY 274614 (2.5 to 20mg/kg i.p.). LY 274614 is an effective neuroprotectant agent against NMDA receptor-induced toxicity when administered systemically and is a promising therapeutic agent for conditions where glutamate plays a role in the pathology of neuronal degeneration.
NPC 12626 的药理学概况，一种新型竞争性 N-甲基-D-天冬氨酸受体拮抗剂。
DOI：
--
发表时间：
1989
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ferkany,JW;Kyle,DJ;Willets,J;Rzeszotarski,WJ;Guzewska,ME;Ellenberger,SR;Jones,SM;Sacaan,AI;Snell,LD;Borosky,S
通讯作者：
Borosky,S
兴奋性氨基酸拮抗剂在鸽子中诱导苯环己哌啶样僵直症：结构活性研究。
影响因子：
4.7
作者：
Koek,W;Woods,JH;Mattson,MV;Jacobson,AE;Mudar,PJ
通讯作者：
Mudar,PJ