PET STUDIES OF THE PHARMACOKINETICS OF D-METHAMPHETAMINE IN THE HUMAN BODY

D-甲基苯丙胺在人体内药代动力学的 PET 研究

• 批准号: 7607918
• 负责人: JOANNA S FOWLER
• 金额: $ 0.4万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-23 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607918
• 关键词: Accounting; Biological; Brain; Carbon; Catecholamines; Classification; Cocaine; Computer Retrieval of Information on Scientific Projects Database; Dopamine; Drug Kinetics; Funding; Grant; Human; Human body; Individual; Institution; Investigation; Isomerism; Kinetics; Label; Laboratories; Laboratory Animals; Measures; Methamphetamine; Neurons; Neurotransmitters; Numbers; Organ; Peripheral; Pharmaceutical Preparations; Positron-Emission Tomography; Public Health; Relative (related person); Research; Research Personnel; Resources; Source; Time; Toxic effect; United States National Institutes of Health; dopamine transporter; presynaptic; uptake; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Methamphetamine is a powerful stimulant drug, which is abused by humans. Methamphetamine abuse has become a significant public health problem not only because it is highly addictive but also because its abuse is associated with significant toxicity to the brain and other organs. The problem is exacerbated by the fact that it is readily synthesized in clandestine laboratories . Methamphetamine's principle pharmacological action is the release of dopamine and other neurotransmitters through the individual neurotransmitter transporters on presynaptic neurons. Methamphetamine-induced dopamine release is high relative to another stimulant drug, cocaine, and dopamine levels remain high over a longer period of time in laboratory animals. This results in an intense long-term stimulant effect, which is also seen in the human methamphetamine abuser. Methamphetamine induced toxicity to the brain and other organs is generally attributed to increased levels of dopamine and other catecholamines which are generally associated with oxidative damage . There are a number of biological and pharmacological factors, which may account for methamphetamine's high addictive potential and for its toxicity. One likely candidate is its pharmacokinetics in the brain and other organs. However, methamphetamine's pharmacokinetics in the human brain and in other organs are not known. Here we propose a systematic investigation of the uptake and kinetics of d-methamphetamine (the active isomer) in the brain and in peripheral organs with PET and carbon-11 labeled d-methamphetamine in a group of normal healthy non-drug abusing volunteers. We will also pair the brain study with a measure of dopamine transporter (DAT) availability using [11C]cocaine to measure DAT levels in the same individuals.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 甲基苯丙胺是一种强效兴奋剂，被人类滥用。 甲基安非他明的滥用已成为一个重大的公共卫生问题，这不仅是因为它极易上瘾，而且还因为它的滥用与对大脑和其他器官的严重毒性有关。 这一问题因其易于在秘密制药厂合成而更加严重。 甲基苯丙胺的主要药理作用是通过突触前神经元上的单个神经递质转运体释放多巴胺和其他神经递质。 相对于另一种兴奋剂可卡因，甲基苯丙胺诱导的多巴胺释放较高，并且在实验室动物中多巴胺水平在较长时间内保持较高。 这导致强烈的长期兴奋作用，这也见于人类甲基苯丙胺滥用者。 甲基苯丙胺对大脑和其他器官的毒性通常归因于多巴胺和其他儿茶酚胺水平的增加，这通常与氧化损伤有关。 有一些生物学和药理学因素可能是甲基苯丙胺高度成瘾性及其毒性的原因。 一个可能的候选者是它在大脑和其他器官中的药代动力学。 然而，甲基苯丙胺在人脑和其他器官中的药代动力学尚不清楚。 在这里，我们提出了一个系统的调查的摄取和动力学的d-甲基苯丙胺（活性异构体）在大脑和外周器官与PET和碳-11标记的d-甲基苯丙胺在一组正常健康的非药物滥用志愿者。 我们还将把大脑研究与使用[11 C]可卡因测量多巴胺转运蛋白（DAT）可用性的措施配对，以测量同一个体的DAT水平。