SYNTHESIS OF PROBES TO MONITOR BRAIN RECEPTOR MOBILITY

监测脑受体迁移性的探针合成

• 批准号: 3509207
• 负责人: John L Neumeyer
• 金额: $ 25.22万
• 依托单位: SIGMA-ALDRICH RESEARCH BIOCHEMICAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3509207
• 关键词: antiparkinson drugs; biotin; brain; chemical binding; chemical conjugate; chemical synthesis; dopamine; dopamine receptor; drug receptors; flow cytometry; fluorescence microscopy; fluorescent dye /probe; inhibitor /antagonist; laboratory rat; ligands; neuropharmacology; neurotransmitters; photochemistry; radiotracer

The objectives of Phase II of this proposal are to continue the development and evaluation of molecular probes for D1 and D2 dopamine receptors. Dysfunctions of brain dopamine systems have been implicated in neurological, psychiatric and endocrine disorders and dopaminergic agents are widely prescribed to alleviate their symptoms. Brain dopamine receptors are the molecular targets of the most effective drugs used in the treatment of schizophrenia and Parkinson's disease. The cellular and subcellular distribution and mobility of these receptors remain poorly understood because the available receptor probes do not provide the resolution or detection capabilities required for this vital research. We propose to synthesize fluorescent and biotin probes for dopamine receptors using antagonist drugs as precursors. We will evaluate the affinity and receptor selectivity at D1 and D2 dopamine receptors, brain distribution and cellular distribution in progressive stages. Receptor- selective molecular probes will permit detection of the receptors by fluorescence, light, and electron microscopy and will be useful for mapping cellular and subcellular distribution of dopamine receptors, prior to and after drug treatment, for monitoring receptor mobility, and cell-sorting of dopamine receptor-containing cells. These novel compounds may expedite a clearer understanding of dopamine receptor function in the diseased state and drug-induced adaptive processes. They may furthermore create novel methodologies in psycho- and neuropharmacology research.

本提案第二阶段的目标是继续发展 以及对D1和D2多巴胺受体分子探针的评价。 脑多巴胺系统的功能障碍被认为与 神经、精神和内分泌障碍与多巴胺能药 被广泛开出用来缓解他们的症状。脑多巴胺 受体是最有效的药物的分子靶点 治疗精神分裂症和帕金森氏症。蜂窝和 这些受体的亚细胞分布和流动性仍然很差。 理解是因为可用的受体探针不提供 这项重要研究所需的分辨率或检测能力。 我们建议合成多巴胺的荧光和生物素探针。 受体使用拮抗剂药物作为前体。我们将评估 脑多巴胺受体D1和D2的亲和力和受体选择性 进展期的分布和细胞分布。受体- 选择性分子探针将允许通过以下方式检测受体 荧光、光和电子显微镜，将有助于测绘 多巴胺受体的细胞和亚细胞分布 在药物治疗后，用于监测受体的流动性和细胞分类 含有多巴胺受体的细胞。这些新化合物可能会加速 更清楚地了解多巴胺受体在疾病状态下的功能 以及药物诱导的适应过程。他们还可以创作小说 心理学和神经药理学研究的方法论。

项目成果

Fluorescent and biotin probes for dopamine receptors: D1 and D2 receptor affinity and selectivity.

多巴胺受体的荧光和生物素探针：D1 和 D2 受体亲和力和选择性。

• 发表时间: 1990
• 期刊: Molecular pharmacology
• 影响因子: 3.6
• 作者: Madras,BK;Canfield,DR;Pfaelzer,C;VittimbergaJr,FJ;Difiglia,M;Aronin,N;Bakthavachalam,V;Baindur,N;Neumeyer,JL
• 通讯作者: Neumeyer,JL