SAFETY ASSESSMENT OF FENFLURAMINE & PHENTERMINE IN HUMANS

芬氟拉明的安全性评估

• 批准号: 6265723
• 负责人: GEORGE A RICAURTE
• 金额: $ 6.52万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265723
• 关键词: anorexic agent; clinical research; combination chemotherapy; drug adverse effect; fenfluramine; human subject; neuroendocrine system; neuropharmacology; serotonin; serotonin transporter

In animals, fenfluramine alone or in combination with phentermine, produces toxic effects on brain serotonin (5-HT) neurons. In particular, the available data indicate that fenfluramine produces a distal axotomy of brain 5-HT neurons in a number of different animal species, including nonhuman primates. Whether fenfluramine also damages 5-HT neurons in humans has not been determined. The purpose of the present project is to determine whether fenfluramine alone or in combination with phentermine, damages brain 5-HT neurons in humans. To this end, we will determine whether subjects with a history of treatment with fenfluramine alone or in combiunation with phentermine, show long-term effects on 5-HT transporter density, CSF 5-HIAA concentration, 5-HT mediated neuroendocrine function, or changes in functional domains in which 5-HT has been implicated (e.g., personality, mood, cognition). These studies are intended to test the hypothesis that fenfluramine/phentermine treatment produces toxic effects on 5-HT neurons in the human brain.

在动物中，芬氟拉明单独或与芬太尼联合使用，会对大脑5-羟色胺(5-HT)神经元产生毒性影响。特别是，现有的数据表明，芬氟拉明在许多不同的动物物种中产生了大脑5-羟色胺神经元的远端轴突切断，包括非人类灵长类动物。芬氟拉明是否也会损害人类的5-羟色胺神经元尚未确定。本项目的目的是确定芬氟拉明单独或与苯丙氨酸联合使用是否会损害人类大脑中的5-羟色胺神经元。为此，我们将确定有芬氟拉明单独治疗史或与芬太尼联合治疗的受试者是否对5-羟色胺转运体密度、脑脊液5-HIAA浓度、5-羟色胺介导的神经内分泌功能或与5-羟色胺相关的功能领域(如个性、情绪、认知)的变化有长期影响。这些研究旨在验证芬氟拉明/芬太尼治疗对人脑5-羟色胺神经元产生毒性影响的假设。