SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS
SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS
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
中文摘要
缺血时神经元的损伤是由谷氨酸的过度释放引起的
从大脑神经末梢。 我们发现,使用新的快速动力学
在P.l.中开发的方法。的实验室,某些替代品
胍类和相关化合物是钙依赖性
从脑神经末梢释放谷氨酸和多巴胺。 其中一
表现出选择性阻断谷氨酸释放。 这些化合物,我们
假设作为突触前钙通道拮抗剂,可能
用作药物,以限制中风和创伤性脑缺血损伤
脑损伤患者 我们的目标是识别和合成额外的
具有改进的效力和特异性的取代的胍衍生物,
阻断神经递质的释放。 为此,我们将采用
分子模拟工具和定量构效关系
分析. 它们的作用机制和拮抗的选择性
突触前钙通道将由电生理学定义,
放射性同位素通量和放射性配体结合技术。 他们将
在中风动物模型中测试神经保护功效,
剑桥神经科学和研究人员合作,
马萨诸塞州总医院和康奈尔医疗中心。 我们的初步
体内研究已经证明了通过取代的胍
阻止神经递质的释放
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)
专著(0)
科研奖励(0)
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:
MOLECULAR STUDIES OF CA++ TRANSPORT IN NERVE AND RETINA
-
批准号:3288136
-
项目类别:
-
资助金额:$8.71万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CA CHANNEL
-
批准号:3288138
-
项目类别:
-
资助金额:$1.43万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CA CHANNEL
-
批准号:3288137
-
项目类别:
-
资助金额:$16.93万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR STUDIES OF CA++ TRANSPORT IN NERVE AND RETINA
-
批准号:3288142
-
项目类别:
-
资助金额:$21.59万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CA CHANNEL
-
批准号:3288135
-
项目类别:
-
资助金额:$17.84万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537213
-
项目类别:
-
资助金额:$10.5万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537215
-
项目类别:
-
资助金额:$10.56万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537217
-
项目类别:
-
资助金额:$20.92万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537216
-
项目类别:
-
资助金额:$20.92万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
海外基金