CLINICAL TRIAL: NEW MEDICATIONS TO TREAT ALCOHOL DEPENDENCE

临床试验：治疗酒精依赖的新药

• 批准号: 7951471
• 负责人: Bankole A Johnson
• 金额: $ 3.51万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951471
• 关键词: Acute; Alcohol dependence; Alcohols; Characteristics; Chronic; Classification; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Controlled Environment; 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 cue; alcohol effect; alcohol reward; alcohol seeking behavior; base; 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. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在过去的十年中，人们对寻求饮酒行为的神经科学基础的新知识爆炸了。 通过促进γ-氨基丁基功能并抑制兴奋性氨基酸的作用，可以可靠地减少酒精的奖励作用，从而调节中唇多巴胺途径的药物。 托吡酯（硫酸盐溶剂丙糖酸衍生物）具有这些特征。 为了支持这一概念，我们在一项II-II型药物临床试验中表明，托吡酯在改善饮酒结果和减少（n = 150）酒精依赖性个体的渴望方面优于安慰剂。 使用人类实验室的经过精心控制的环境，我们使用一组系统研究来直接评估与托吡酯在酒精依赖性个体中与托吡酯的抗喝作用相关的机械性神经药物过程。 这将为寻求酒精行为的神经生物学提供更全面的理解，并有助于开发更有效的化合物来治疗酒精依赖性。 因此，该项目的具体目的是：1）确定托吡氨甲酸酯的急性效应剂量关系减少与其滥用和成瘾潜力相关的酒精效应，2）确定是否会急性剂量的托托吡酯剂量的长期治疗是否会导致与酒精相关的提示诱导的渴望，从而减少与酒精相互作用的潜力，并确定与酒精相互作用的相互作用，并确定与酒精相互作用的相互作用，并确定与酒精相互作用的可能性。损害。