BRAIN SEROTONIN SYNTHESIS IN PATIENTS WITH ADDICTIVE AND AGGRESSIVE BEHAVIORS

有成瘾和攻击行为的患者的大脑血清素合成

• 批准号: 6160336
• 负责人: D HOMMER
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160336
• 关键词: Macaca mulatta; aggression; alcoholism /alcohol abuse; brain metabolism; cerebrospinal fluid; drug design /synthesis /production; hydroxyindoleacetate; impulsive behavior; laboratory mouse; laboratory rabbit; mental disorder diagnosis; pharmacokinetics; positron emission tomography; radiopharmacology; radiotracer; serotonin; tryptophan analog

This project is designed to develop and implement a novel positron emitting tracer 11-C-alpha-methyl-tryptophan (CAMT) in order to measure the local distribution and accumulation of brain serotonin in patients with alcoholism, varying degrees of aggressive/impulsive behavior, and normal volunteers. CAMT is currently not approved for human use in the United States. In order to develop CAMT for humans, we must provide toxicology and dosimetry data that fulfill Food and Drug Administration (FDA) and Radiation Safety Committee guidelines, gather kinetic data in higher animals, and modify the synthesis to produce the L-form of CAMT. The pre-clinical toxicology in rabbits and mice has been completed. The dosimetry studies in Rhesus macaques to measure individual organ exposure to CMAT have also been completed. The synthesis of L-CAMT is now running well and sufficient quantities of L-CAMT can be produced. Preliminary to using L-CAMT in humans we have been performing L-CAMT PET scans on 12 rhesus monkeys. These monkeys are animals whose social behavior has been observed and rated since birth. In addition, multiple CSF samples have been analyzed for serotonin metabolites (5-HIAA) in all these animals. The results of these studies show that use of the L-CAMT method for determining serotonin synthesis rates has several serious methodological and theoretical shortcomings which preclude the use of this method in humans; for this reason this project is being terminated. See report Z01 AA 00098-01 LCS for details.

该项目旨在开发和实施一种新型正电子 发射示踪剂 11-C-α-甲基-色氨酸 (CAMT) 以进行测量 患者脑内血清素的局部分布和积累 酗酒、不同程度的攻击性/冲动行为，以及 普通志愿者。 CAMT 目前在美国尚未获准用于人类。 在 为了为人类开发 CAMT，我们必须提供毒理学和 满足食品和药物管理局 (FDA) 要求的剂量测定数据以及 辐射安全委员会指南，收集更高级别的动力学数据 动物，并修改合成以产生 L 型 CAMT。 这 兔子和小鼠的临床前毒理学研究已经完成。 这 恒河猴剂量测定研究，测量个体器官暴露量 至CMAT也已完成。 L-CAMT的合成正在进行中 可以生产良好且足够量的L-CAMT。 初步的 为了在人类中使用 L-CAMT，我们已经对 12 名患者进行了 L-CAMT PET 扫描 恒河猴。 这些猴子的社会行为已被 自出生起就进行观察和评分。 此外，多个脑脊液样本 对所有这些动物的血清素代谢物 (5-HIAA) 进行了分析。 这些研究结果表明，使用 L-CAMT 方法 确定血清素合成率有几个重要的方法论 以及理论上的缺陷，阻碍了该方法的使用 人类；因此，该项目即将终止。 参见报告Z01 AA 00098-01 LCS 了解详细信息。