MEASUREMENT OF NOREPINEPHRIN AND THE METABOLITES IN VARIOUS BODY COMPARTMENTS

去甲肾上腺素和身体各部位代谢物的测量

• 批准号: 3821243
• 负责人: E A LANE
• 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/3821243
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; alcoholism /alcohol abuse; blood chemistry; cerebrospinal fluid; dopamine; drug withdrawal; high risk behavior /lifestyle; homovanillate; human subject; human tissue; indoleacetate; liver metabolism; neurotransmitter metabolism; neurotransmitters; norepinephrine; normetanephrine; serotonin; urinalysis

Attempts to characterize neurotransmitter systems in man have focused on quantification of seronin (5HT), norepinephrine (NE), dopamine (DA), and several metabolites of these monoamines in various body fluids (urine, plasma, CSF). These neurotransmitter systems are suspected to be functioning abnormally in a variety of disorders (alcoholism, depression, schizophrenia, etc). In order to understand the meaning of measuring concentrations of neurotransmitters and their metabolites, it is necessary to understand their pharmacokinetics in different body compartments. a) Plasma and CSF concentrations, as well as 24 hour urinary measures of NE, DA and 5HT and their metabolites (VMA, MHPG, NM, 5HIAA, HVA) were collected in placebo treated, depressed subjects, alcoholics, pathalogical gamblers, and healthy volunteers. Samples were also collected in depressed subjects following treatment with antidepressants. Utilizing these data, a model was formulated which describes the disposition of MHPG. b) Rat liver perfusion using two NE metabolites, NM and MHPG, have been used to determine the fraction of a metabolite being transformed by each of several metabolic pathways. A better understanding of these relationships will help identify differences in formation, metabolism and elimination of these neurotransmitters in humans. This will offer insight into the functioning of these systems, and into the abnormalities of function that result in the previously observed abnormal concentrations of these neurotransmitters and their metabolites in certain disease states such as alcoholism and alcohol withdrawal.

试图描述人类神经递质系统的特征， 集中于血清素（5 HT），去甲肾上腺素（NE）， 多巴胺（DA），以及这些单胺的几种代谢产物， 各种体液（尿液、血浆、CSF）。 这些神经递质 系统被怀疑在各种情况下功能异常， 精神障碍（酗酒、抑郁、精神分裂症等）。 为了 了解测量浓度的意义 神经递质及其代谢物，有必要 了解它们在不同体内的药代动力学 隔间 a）血浆和CSF浓度，以及24 NE、DA和5 HT及其代谢产物的小时尿测量 (VMA、MHPG、NM、5HIAA、HVA） 治疗，抑郁症患者，酗酒者，病态赌徒， 健康志愿者 样本也收集在抑郁症 受试者接受抗抑郁药治疗后。 利用 根据这些数据，制定了一个模型，描述了 MHPG的处置。 B）使用两种NE的大鼠肝脏灌注 代谢产物NM和MHPG已用于确定 代谢物的一部分被几种 代谢途径 更好地了解这些 关系将有助于识别形成的差异， 代谢和消除这些神经递质在人类。 这将使人们深入了解这些系统的运作情况， 导致之前的 观察到这些神经递质的异常浓度， 它们在某些疾病状态下的代谢产物，如酒精中毒， 戒酒