Perampanel Treatment of Alcohol Use Disorder

该项目旨在满足开发更好的药物治疗的迫切需要 酒精使用障碍（AUD）是一个重大的公共卫生问题。这项研究将测试 perampanel，最近FDA批准的抗惊厥药物，以确定其 通过“酒精挑战”模式治疗酒精中毒的临床有效性， 一个小型的临床试验人类酒精挑战实验室研究是一种有效的， 一种负担得起的方法来筛选药物对酒精中毒治疗的有用性， 进行更大规模的临床试验在这个范例中，受试者被给予药物 perampanel（高剂量、低剂量或安慰剂剂量，在后续激发时 天），然后静脉注射乙醇，看看药物是否减少 酒精的奖励和强化作用。拟议的研究将是第一个 在开发perampanel治疗AUD的一系列研究中进行实验。我们将 还进行了一项非常小的开放标签的试点研究的药物，以探索疗效， perampanel治疗AUD受试者样本的可行性。Perampanel工程 主要作为一种选择性的、非竞争性的谷氨酸能AMPA受体拮抗剂， 这使得它在神经药理学设备中非常独特。 对酒精中毒和其他成瘾动物模型的临床前研究表明， AMPA受体拮抗剂减少饮酒和成瘾药物的复发。如果 perampanel被证明可降低酒精对人体的奖赏和强化作用， 并在试点研究中减少饮酒，这将为更多的研究提供强有力的理由。 这种药物的临床试验

This project aims to meet the urgent need for developing better medications to treat alcohol use disorder (AUD), a major public health problem. The proposed study will test perampanel, a recently FDA approved anticonvulsant medication, to determine its clinical usefulness in treating alcoholism via an “alcohol challenge” paradigm paired with a small pilot clinical trial. Human alcohol challenge laboratory studies are an efficient and affordable way to screen medications for their usefulness in alcoholism treatment prior to performing a larger clinical trial. In this paradigm, subjects are given the medication perampanel (at either a high dose, low dose, or placebo dose, on subsequent challenge days), and then are administered intravenous ethanol to see if the medication reduces the rewarding and reinforcing effects of alcohol. The proposed study would be the first experiment in a line of research developing perampanel as a treatment for AUD. We will also conduct a very small open-label pilot study of the medication to explore efficacy and feasibility of perampanel treatment in a sample of subjects with AUD. Perampanel works primarily as a selective, non-competitive glutamatergic AMPA receptor antagonist, a property that makes it quite unique in the neuropharmacologic armamentarium. Preclinical research in animal models of alcoholism and other addictions suggests that AMPA receptor antagonists reduce drinking and relapse to addictive drugs. If perampanel proves to reduce the rewarding and reinforcing effects of alcohol in humans, and reduces drinking in the pilot study, it would provide a strong rationale for more definitive clinical trials with this medication.