SYNTHESIS OF PROBES TO MONITOR BRAIN RECEPTOR MOBILITY

大脑中的多巴胺系统功能障碍一直是 与内分泌、神经和精神疾病有关， 多巴胺能药物被广泛用于治疗这些疾病。 脑多巴胺受体清楚地被认为是 这些毒品。这些受体处于移动的、动态的状态 可以受到药物、损伤、疾病、激素和其他因素的调节 挑战。例如，精神分裂症患者的死后大脑 帕金森患者的多巴胺受体水平发生了变化， 多巴胺药物治疗和/或疾病的后果 各州。尽管多巴胺受体调节的结束状态 通过药物治疗已被描述，对其知之甚少 药物诱导受体适应过程的细胞机制。 在项目的第一阶段，我们建议合成荧光 探针法作为监测多巴胺受体的新方法 脑膜的流动性。荧光化合物将是 与多巴胺激动剂(治疗帕金森病的药物)相结合 药物)和拮抗剂(治疗精神分裂症的药物)。 我们将测试这些化合物的亲和力和选择性 多巴胺受体。不同水平组织的神经膜 因此，组织将暴露在荧光中 激光光漂白的探头及其回收 荧光将通过荧光显微镜进行监测。这些 化合物将提供有关流动性的急需信息 被治疗药物占据的多巴胺。

Dysfunction of dopamine systems in the brain have been implicated in endocrine, neurological and psychiatric disorders, and dopaminergic drugs are widely prescribed for these disorders. Brain dopamine receptors are clearly implicated as the targets of these drugs. These receptors are in a mobile, dynamic state and can, be modulated by drugs, lesions, diseases, hormones and other challenges. For example, post-mortem brains of schizophrenic and Parkinson patients have altered levels of dopamine receptors, a consequence of dopamine drug therapies and/or the disease states. Although the end status of dopamine receptor modulation by drug treatment has been described, little is known about the cellular mechanism of drug-induced receptor adaptive processes. In Phase I of the project we propose to synthesize fluorescent probes as a novel approach to monitoring dopamine receptor mobility in brain membranes. Fluorescent compounds will be coupled to dopamine agonists (therapeutic drugs for Parkinson's disease) and antagonists (therapeutic agents for schizophrenia). We will test the affinity and selectivity of these compounds for dopamine receptors. Neural membranes at various levels of tissue organization will consequently be exposed to the fluorescent probe, photobleached by laser beam, and the recovery of fluorescence will be monitored by fluorescent microscopy. These compounds will provide much needed information on the mobility of dopamine occupied by therapeutic drugs.