Trials of Medications for Stimulant Abuse Research Plan

兴奋剂滥用药物试验研究计划

• 批准号: 6825061
• 负责人: Thomas Frederick Newton
• 金额: $ 29.46万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6825061
• 关键词: ACE inhibitors; antihypertensive agents; cardiovascular function; central nervous system stimulants; cholinesterase inhibitors; clinical trial phase I; combination chemotherapy; craving; dopamine agonists; drug abuse; drug abuse chemotherapy; drug design /synthesis /production; drug screening /evaluation; gamma aminobutyrate; human subject; human therapy evaluation; methamphetamine; muscle relaxants; neurotransmitter agonist; patient oriented research; pharmacokinetics; placebos; psychopharmacology; reinforcer; substance abuse related behavior

Phase I Trials: We have developed an integrated research program to efficiently and comprehensively identify, evaluate, and develop pharmacotherapeutic treatments for methamphetamine abuse and dependence. A key component of this program is a Phase I human clinical laboratory capable of performing interaction studies needed for assessment of safety and potential efficacy for medications under consideration for study in subsequent Phase II trials. We propose to further develop this research capacity in order to focus on medications or combinations of medications with novel mechanisms of action for the treatment of stimulant abuse and dependence, focusing on methamphetamine. The series of Phase I studies proposed in this project application as a component of the P50 Center continuation will address the following Specific Aims: Aim 1: To determine how treatment with an active medication, compared to placebo, alters cardiovascular effects produced by methamphetamine; Aim 2: To determine how treatment with an active medication, compared to placebo, alters subjective and reinforcing effects produced by methamphetamine; Aim 3: To determine how treatment with an active medication, compared to placebo, alters craving and drug-seeking behavior produced by methamphetamine. A total of four double-blind placebo-controlled studies over five years are planned. Medications to be studied include the cholinesterase inhibitor rivastigmine and the dopamine partial agonist aripiprazole combined with the GABA B agonist baclofen. Two additional studies will be designed based on the outcome of the first two studies and based on scientific developments emerging in the interim to provide safety and preliminary efficacy data for a 3rd phase II trial. A procedure is described for considering evaluation of perindopril and agents acting at the GABA transporter, (tiagabine), that are being studied elsewhere currently for cocaine dependence or other dopamine partial agonists, glutamatergic agents, or compounds from new classes that may be available.

第一阶段试验：我们制定了一项综合研究计划，以有效、全面地识别、评估和开发针对甲基苯丙胺滥用和依赖的药物治疗方法。该计划的一个关键组成部分是一期人体临床实验室，能够进行相互作用研究，以评估后续二期试验中考虑研究的药物的安全性和潜在功效。我们建议进一步发展这种研究能力，以便重点研究具有新作用机制的药物或药物组合，用于治疗兴奋剂滥用和依赖性，重点是甲基苯丙胺。作为 P50 中心延续的一部分，本项目申请中提出的一系列第一阶段研究将解决 具体目标如下： 目标 1：确定与安慰剂相比，活性药物治疗如何改变甲基苯丙胺产生的心血管效应；目标 2：确定与安慰剂相比，活性药物治疗如何改变甲基苯丙胺产生的主观作用和强化作用；目标 3：确定与安慰剂相比，活性药物治疗如何改变甲基苯丙胺产生的渴望和寻求药物的行为。计划在五年内进行总共四项双盲安慰剂对照研究。待研究的药物包括胆碱酯酶抑制剂卡巴拉汀和多巴胺部分激动剂阿立哌唑联合 GABA B 激动剂巴氯芬。将根据前两项研究的结果设计另外两项研究 在此期间出现的科学进展，为第三次二期试验提供安全性和初步疗效数据。描述了考虑评估培哚普利和作用于 GABA 转运蛋白（噻加宾）的药物的程序，目前正在其他地方研究可卡因依赖或其他多巴胺部分激动剂、谷氨酸药物或可能可用的新类别化合物。