NEW MEDICATIONS TO TREAT ALCOHOL DEPENDENCE

治疗酒精依赖的新药物

• 批准号: 7606703
• 负责人: Bankole A Johnson
• 金额: $ 41.16万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606703
• 关键词: Acute; Alcohol dependence; Alcohols; Characteristics; Chronic; Classification; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Controlled Environment; Cues; Development; Dopamine; Dose; Excitatory Amino Acids; Explosion; Funding; Grant; Human; Impairment; Individual; Institution; Knowledge; Laboratories; Neurobiology; Neurocognitive; Outcome; Pathway interactions; Pharmaceutical Preparations; Phase; Placebos; Process; Relapse; Research; Research Personnel; Resources; Source; United States National Institutes of Health; addiction; alcohol effect; alcohol reward; alcohol seeking behavior; base; concept; craving; drinking; improved; sulfamate; topiramate

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. In the last decade, there has been an explosion of new knowledge of the neuroscientific basis of alcohol-seeking behavior. Briefly, medications that modulate mesolimbic dopamine pathways by facilitating gamma-aminobutyric function and inhibiting the action of excitatory amino acids should reliably diminish alcohol's rewarding effects. Topiramate (a sulfamate-substituted fructopyranose derivative) has these characteristics. In support of this concept, we have shown in a phase-II-type medications clinical trial that topiramate is significantly superior to placebo at improving drinking outcomes and decreasing craving among (N = 150) alcohol-dependent individuals. Using the carefully controlled environment of the human laboratory, we are using a set of systematic studies to assess directly the mechanistic neuropharmacological processes that are associated with topiramate's anti-drinking effects in alcohol-dependent individuals. This will provide a more comprehensive understanding of the neurobiology of alcohol-seeking behavior and aid in the development of even more effective compounds for the treatment of alcohol dependence. Thus, the specific aims of the project are to: 1) determine the dose relationship of acute effects of topiramate to reduce alcohol effects related to its abuse and addiction potential, 2) determine whether chronic treatment with an acutely effective dose of topiramate produces substantial reductions in alcohol-related cue-induced craving, thereby decreasing the potential for treatment relapse, and 3) determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在过去的十年中，关于酗酒行为的神经科学基础的新知识不断涌现。 简而言之，通过促进γ-氨基丁酸功能和抑制兴奋性氨基酸的作用来调节中脑边缘多巴胺通路的药物应该可靠地减少酒精的奖励作用。 托吡酯（一种氨基磺酸酯取代的吡喃果糖衍生物）具有这些特性。 为了支持这一概念，我们在一项 II 期药物临床试验中表明，托吡酯在改善饮酒结果和降低（N = 150）酒精依赖者的渴望方面明显优于安慰剂。 利用精心控制的人类实验室环境，我们正在使用一系列系统研究来直接评估与托吡酯对酒精依赖个体的抗饮酒作用相关的机制神经药理学过程。 这将使人们更全面地了解酗酒行为的神经生物学，并有助于开发更有效的治疗酒精依赖的化合物。 因此，该项目的具体目标是：1) 确定托吡酯的急性作用的剂量关系，以减少与其滥用和成瘾潜力相关的酒精作用，2) 确定使用急性有效剂量的托吡酯进行长期治疗是否会产生实质性的减少减少与酒精相关的线索诱发的渴望，从而降低治疗复发的可能性，3) 确定托吡酯与酒精和不与酒精的相互作用是否与神经认知障碍有关。