AROMATIC L AMINO ACID DECARBOXYLASE STUDIES IN VIVO

芳香族 L 氨基酸脱羧酶体内研究

• 批准号: 6194212
• 负责人: Onofre DeJesus
• 金额: $ 43.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6194212
• 关键词: MAO inhibitors; Macaca mulatta; age difference; amine oxidase (flavin); aminoacid metabolism; aromatic L aminoacid decarboxylase; brain metabolism; clinical research; decarboxylase inhibitor; endocrine neoplasm; enzyme activity; human subject; laboratory mouse; laboratory rat; longitudinal animal study; magnetic resonance imaging; pharmacokinetics; positron emission tomography; reagent /indicator; tyrosine analog

This is a competing continuation of grant RO1-NS26621. The investigators have interest in neurotransmitters specifically the aromatic L-amino acid Decarboxylase (AAAD) enzyme, which is involved in the synthesis of dopamine, norepinephrine, and serotonin. The main objective is to develop PET imaging for in vivo assessment of AAAD. They have developed an imaging agent 6-fluoro-m-tyrosine (6FMT), which is taken up into monoaminergic neurons and decarboxylated by AAAD to form metabolites, which do not egress from the brain. The Specific Aims are: 1) to study 6FMT PET imaging and AAAD activity in rhesus monkey, 2) to study sensitivity and reproducibility issues in humans, and 3) to develop new 6FMT derivative as peripheral AAAD imaging agent. The PET studies will assess the scope and limitation of this technique as a method to evaluate AAAD in the study of neuropsychiatric disorders involving dopamine, nor epinephrine and serotonin. The in vivo imaging technique may assist in understanding etiologies of neuropsychiatric disorders such as Parkinson's disease, schizophrenia, substance abuse, anxiety and bipolar disorders.

这是Grant RO1-NS26621的竞争延续。这 研究人员对神经递质特别是芳香族的兴趣 L-氨基酸脱羧酶（AAAD）酶，参与合成 多巴胺，去甲肾上腺素和5-羟色胺。主要目的是开发宠物 对AAAD的体内评估进行成像。他们已经开发了成像剂 6-氟-m-酪氨酸（6FMT），将其摄入单胺能神经元和 由AAAD脱羧以形成代谢物，不会从大脑中流出。 具体目的是：1）研究恒河猴中的6FMT PET成像和AAAD活动 猴子，2）研究人类的敏感性和可重复性问题，3） 开发新的6FMT衍生物作为外围AAAD成像剂。宠物研究 将评估该技术的范围和限制作为评估的方法 在涉及多巴胺的神经精神疾病的研究中 肾上腺素和5-羟色胺。体内成像技术可能有助于 了解神经精神疾病的病因，例如帕金森氏症 疾病，精神分裂症，药物滥用，焦虑和躁郁症。