课题基金 / 基金详情

SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS

SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS
合成神经保护谷氨酸释放阻滞剂
批准号:
3504569
负责人:
STANLEY M GOLDIN
金额:
$5.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1991
资助国家:
美国
项目状态:
已结题
起止时间:
1991-12-17 至 1992-06-17

项目摘要

项目成果

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中文摘要
翻译
缺血时神经元损伤是由谷氨酸过度释放引起的
英文摘要
Neuronal damage in ischemia is initiated by excessive release of glutamate from brain nerve terminals. We have discovered, using novel rapid kinetic methodology developed in the P.l.'s laboratory, that certain substituted guanidines and related compounds are antagonists of calcium-dependent release of glutamate and dopamine from brain nerve terminals. One of these exhibits selective block of glutamate release. Such compounds, which we hypothesize to act as antagonists of presynaptic calcium-channels, may be employed as drugs to limit ischemic brain damage in stroke and traumatic brain injury patients. Our goal is to identify and synthesize additional substituted guanidine derivatives of improved potency and specificity for blockade of neurotransmitter release. To that end, we will employ molecular modeling tools and quantitative structure activity relationship analysis. Their mechanism of action and selectivity for antagonism of presynaptic calcium channels will be defined by electrophysiological, radioisotopic flux, and radioligand binding techniques. They will be tested for neuroprotective efficacy in animal models of stroke, both at Cambridge NeuroScience and in collaboration with investigators at the Massachusetts General Hospital and Cornell Medical Center. Our preliminary in vivo studies have demonstrated neuroprotection by substituted guanidines which block neurotransmitter release.
期刊论文(1)
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会议论文
Neuroprotective use-dependent blockers of Na+ and Ca2+ channels controlling presynaptic release of glutamate.
神经保护性使用依赖的 Na 和 Ca2 通道阻滞剂控制突触前谷氨酸的释放。
DOI: 10.1111/j.1749-6632.1995.tb16578.x
发表时间: 1995
期刊: Annals of the New York Academy of Sciences
影响因子: 5.2
作者: [Goldin,SM, Subbarao,K, Sharma,R, Knapp,AG, Fischer,JB, Daly,D, Durant,GJ, Reddy,NL, Hu,LY, Magar,S]
通讯作者: Magar,S
SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS
  • 批准号:
    3509292
  • 项目类别:
  • 资助金额:
    $25.0万
  • 财政年份:
    1991
  • 负责人:
    STANLEY M GOLDIN
  • 依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CHANNEL
  • 批准号:
    3288141
  • 项目类别:
  • 资助金额:
    $11.5万
  • 财政年份:
    1989
  • 负责人:
    STANLEY M GOLDIN
  • 依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CHANNEL
  • 批准号:
    3288140
  • 项目类别:
  • 资助金额:
    $27.2万
  • 财政年份:
    1989
  • 负责人:
    STANLEY M GOLDIN
  • 依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CHANNEL
  • 批准号:
    3288139
  • 项目类别:
  • 资助金额:
    $22.71万
  • 财政年份:
    1989
  • 负责人:
    STANLEY M GOLDIN
  • 依托单位:
海外基金