SAFETY ASSESSMENT OF FENFLURAMINE & PHENTERMINE IN HUMANS

在动物中，芬氟拉明单独或与芬特明组合，对脑5-羟色胺（5-HT）神经元产生毒性作用。特别是，现有数据表明，芬氟拉明在许多不同的动物物种（包括非人类灵长类动物）中引起大脑5-HT神经元的远端轴突切断。芬氟拉明是否也会损害人类的5-HT神经元尚未确定。本项目的目的是确定芬氟拉明单独或与芬特明组合是否损害人类大脑5-HT神经元。本 最后，我们将确定是否与芬氟拉明单独或与芬特明联合治疗史的受试者，显示长期效果 对5-HT转运蛋白密度、CSF 5-HIAA浓度、5-HT介导的神经内分泌功能或涉及5-HT的功能结构域的变化（例如，个性、情绪、认知）。这些研究旨在检验芬氟拉明/芬特明治疗对人脑中5-HT神经元产生毒性作用的假设。

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.