NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
批准号:
6323407
负责人:
ELIZABETH D. ABERCROMBIE
金额:
$20.73万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-05-01 至 2001-04-30
关键词:
6 hydroxydopamine Parkinson's disease antiparkinson drugs brain disorder chemotherapy corpus striatum dihydroxyphenylalanine dopamine dopamine antagonists dopamine receptor drug adverse effect drug tolerance environmental stressor experimental brain lesion high performance liquid chromatography laboratory rat longitudinal animal study microdialysis nervous system disorder diagnosis neurochemistry neurons neuropharmacology neurotransmitter biosynthesis nonhuman therapy evaluation pharmacokinetics substantia nigra video recording system
中文摘要
拟议研究的长期目标是了解,
在生化水平上,卓越的初始水平的基础
L多巴改善慢性阻塞性肺疾病的疗效观察
帕金森氏症的症状。此外,我们希望确定
导致最终结果的潜在机制
帕金森病患者对L-多巴的耐受性下降
由于通常在五到八点之后出现的不良副作用
多年来一直服用这种药物。尽管它作为一种治疗药物的缺点
经纪人L-多巴仍然是最有效和使用最广泛的
治疗帕金森症候群的化合物。变得更好
了解与有益的AS相关的神经生物学
对于L-多巴的不良行为,我们将增加
对这种疾病的了解,然后可以应用于
制定改进的治疗策略。此外,这样的
信息将有助于我们理解这两种正常情况
和基底神经节功能紊乱。建议数
研究将利用6-OHDA处理的大鼠作为动物模型
帕金森氏症。体内微透析,一种使
重复测量细胞外神经递质水平以
在清醒的动物身上进行,将被用来确定
给药后纹状体多巴胺释放的特点
L-多巴对帕金森病早期动物模型的研究
疾病时黑质纹状体多巴胺的丢失只是部分。
这些数据将与之前在
模拟疾病最后阶段的动物,当黑质纹状体
多巴胺的退化已接近完成。我们还建议
探索药理操控的可能性
纹状体5-羟色胺的神经支配,在晚期相对较少
帕金森氏症的阶段,可以提供一种手段来提供
L多巴在体内形成多巴胺的生理来源
严重耗尽多巴胺的动物,这种方法
可能最终被证明是有用的,以绕过
突发的、不受欢迎的副作用。最后,我们建议评估
多巴胺在基底节外部位的作用
纹状体主要靶区对生化效应的影响
为了理解这个动物模型中出现的L-多巴
这种化合物在基底神经节中的作用
电路作为一个整体。
英文摘要
The long-term objective of the proposed research is to understand,
at the biochemical level, the basis for the remarkable initial
efficacy of L-DOPA as a therapeutic agent for ameliorating the
symptoms of Parkinson's disease. Further, we wish to determine
the underlying mechanisms that are responsible for the eventual
decline in the ability of Parkinsonian patients to tolerate L-DOPA
due to unwanted side effects that emerge usually after five to eight
years of taking the drug. Despite its shortcomings as a therapeutic
agent, L-DOPA remains the most efficacious and widely utilized
compound for treating Parkinsonian symptomatology. By better
understanding the neurobiology associated with the beneficial as
well as the undesirable actions of L-DOPA we will increase our
knowledge of this disorder which then ca be applied to the
development of improved therapeutic strategies. In addition, such
information will contribute to our understanding of both normal
and disordered functioning of the basal ganglia. The proposed
studies will utilize the 6-OHDA treated rat as an animal model of
Parkinson's disease. In vivo microdialysis, a method enabling
repeated measurements of extracellular neurotransmitter levels to
be conducted in awake animals, will be employed to determine the
characteristics of striatal dopamine release after administration of
L-DOPA to animals modelling the early stage of Parkinson's
disease when the loss of nigrostriatal dopamine is only partial.
These data will be compared to previous results obtained in
animals modelling the final stage of the disorder when nigrostriatal
dopamine degeneration is nearly complete. We also propose to
explore the possibility that pharmacological manipulation of the
striatal serotonin innervation, which is relatively spared in the late
stage of Parkinsonism, may provide means to supply a
physiological source of dopamine formed from L-DOPA in
severely dopamine-depleted animals and that such an approach
may ultimately prove useful for circumventing the problem of
emergent, unwanted side effects. Finally, we propose to evaluate
the contribution of dopamine acting at basal ganglia sites outside
of the primary target region in striatum to the biochemical effects
of L-DOPA that occur in this animal model in order to understand
the actions of this compound in the context of the basal ganglia
circuitry as a whole.
期刊论文(0)
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会议论文
10th Triennial Meeting of the International Basal Ganglia Society
-
批准号:7915052
-
项目类别:
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资助金额:$2.0万
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财政年份:2010
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负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
Basal Ganglia Functions in Huntington's Disease: Genetic Mouse Models
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批准号:7578753
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项目类别:
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资助金额:$33.8万
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财政年份:2008
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负责人:ELIZABETH D. ABERCROMBIE
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依托单位:
Basal Ganglia Functions in Huntington's Disease: Genetic Mouse Models
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批准号:8096619
-
项目类别:
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资助金额:$33.12万
-
财政年份:2008
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负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
Basal Ganglia Functions in Huntington's Disease: Genetic Mouse Models
-
批准号:7888158
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项目类别:
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资助金额:$33.46万
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财政年份:2008
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负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
Basal Ganglia Functions in Huntington's Disease: Genetic Mouse Models
-
批准号:8289648
-
项目类别:
-
资助金额:$33.12万
-
财政年份:2008
-
负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
Basal Ganglia Functions in Huntington's Disease: Genetic Mouse Models
-
批准号:7692284
-
项目类别:
-
资助金额:$33.8万
-
财政年份:2008
-
负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
-
批准号:6610369
-
项目类别:
-
资助金额:$20.73万
-
财政年份:2001
-
负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
-
批准号:6448230
-
项目类别:
-
资助金额:$20.73万
-
财政年份:2001
-
负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
-
批准号:6302742
-
项目类别:
-
资助金额:$12.18万
-
财政年份:2000
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负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
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批准号:6217903
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项目类别:
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资助金额:$12.18万
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财政年份:1999
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负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
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批准号:6112188
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项目类别:
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资助金额:$12.18万
-
财政年份:1999
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负责人:ELIZABETH D. ABERCROMBIE
-
依托单位:
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
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批准号:6273675
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项目类别:
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资助金额:$11.52万
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财政年份:1998
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负责人:ELIZABETH D. ABERCROMBIE
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依托单位:
NEUROCHEMISTRY OF THERAPEUTICS IN PARKINSON'S DISEASE
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批准号:6243527
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项目类别:
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资助金额:$9.01万
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财政年份:1997
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负责人:ELIZABETH D. ABERCROMBIE
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依托单位:
NEUROCHEMICAL PLASTICITY AND DRUG RESPONSES--AMPHETAMINE
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批准号:2331160
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项目类别:
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资助金额:$15.0万
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财政年份:1993
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依托单位:
NEUROCHEMICAL PLASTICITY AND DRUG RESPONSES--AMPHETAMINE
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批准号:2120562
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项目类别:
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资助金额:$14.42万
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财政年份:1993
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负责人:ELIZABETH D. ABERCROMBIE
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依托单位:
NEUROCHEMICAL PLASTICITY AND DRUG RESPONSES--AMPHETAMINE
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批准号:3214659
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项目类别:
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资助金额:$15.23万
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财政年份:1993
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负责人:ELIZABETH D. ABERCROMBIE
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依托单位:
NEUROCHEMICAL PLASTICITY AND DRUG RESPONSES--AMPHETAMINE
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批准号:2120561
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项目类别:
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财政年份:1993
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负责人:ELIZABETH D. ABERCROMBIE
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依托单位:
NEUROCHEMICAL PLASTICITY AND DRUG RESPONSES--AMPHETAMINE
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批准号:2120560
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项目类别:
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财政年份:1993
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负责人:ELIZABETH D. ABERCROMBIE
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批准号:3052902
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资助金额:$1.83万
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财政年份:1990
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负责人:ELIZABETH D. ABERCROMBIE
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依托单位:
STRESS & ADAPTIVE PROPERTIES OF NORADRENERGIC SYSTEMS
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