NK1 receptor antagonism for treatment of alcohol-dependent patients

NK1受体拮抗剂治疗酒精依赖患者

基本信息

项目摘要

Alcohol dependence is highly co-morbid with anxiety disorders. Urges to drink are closely correlated with concomitant levels of self-reported anxiety. Substance P, released in the amygdala in response to stress, acts at neurokinin 1 (NK1) receptors to mediate the anxiogenic effects of stress. Blockade of the NK1 receptor subtype represents a novel approach to reduce stress-induced negative affect. Preliminary data obtained from NK1 null-mutant animals shows a decrease in voluntary intake of alcohol. The study was carried out in 50 anxious (defined by a Spielberger Trait Anxiety Score of >39) inpatients with a diagnosis of alcohol dependence. A one week placebo lead-in was used. During this time, a baseline, unmedicated alcohol cue reactivity session was carried out to exclude placebo responders and subjects who did not report craving in response to the alcohol cue. Subjects who were cure-reactive on the baseline session were randomized into the double-blind study, in which participants received either 50 mg of an NK1 antagonist or placebo. The duration of active treatment was approximately 3 weeks. Outcome variables designed to test drug efficacy included: 1) rating scales for anxiety and craving; 2) response to alcohol cues presented in the clinic as well as alcohol and non-alcohol containing beverage images paired with positive or negative IAPS images in the fMRI scanner; and 3) response to psychological (Trier Test) and physiological stressors (Metyrapone Tests). This study has been completed and analyses show that a number of the measures are predictive of clinical efficacy. A manuscript based on the findings of the study has been published in Science.
酒精依赖与焦虑症高度共病。 喝酒的冲动与自我报告的焦虑水平密切相关。 P物质,在应激时在杏仁核中释放,作用于神经激肽1(NK 1)受体,介导应激的焦虑效应。 阻断NK 1受体亚型代表了一种减少压力诱导的负面影响的新方法。 从NK 1零突变动物获得的初步数据显示,自愿摄入酒精的减少。 该研究在50名诊断为酒精依赖的焦虑(由Spielberger特质焦虑评分>39定义)住院患者中进行。 使用一周的安慰剂导入。 在此期间,进行基线、未加药的酒精提示反应会话,以排除安慰剂应答者和未报告对酒精提示有渴望的受试者。 在基线治疗中有治愈反应的受试者被随机分配到双盲研究中,其中参与者接受50 mg的NK 1拮抗剂或安慰剂。 活性治疗的持续时间约为3周。 设计用于测试药物功效的结果变量包括:1)焦虑和渴望的评定量表; 2)对诊所中呈现的酒精提示以及与fMRI扫描仪中的阳性或阴性IAPS图像配对的含酒精和不含酒精的饮料图像的反应;和3)对心理(特里尔测试)和生理应激源(甲吡酮测试)的反应。 这项研究已经完成,分析表明,一些措施是预测临床疗效。 基于这项研究结果的手稿已发表在《科学》杂志上。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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David T George其他文献

The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects
焦虑型酒精依赖女性中的 CRF1 拮抗剂 Verucerfont:神经内分泌的翻译,但不是抗渴望效应的翻译
  • DOI:
    10.1038/npp.2016.61
  • 发表时间:
    2016-04-25
  • 期刊:
  • 影响因子:
    7.100
  • 作者:
    Melanie L Schwandt;Carlos R Cortes;Laura E Kwako;David T George;Reza Momenan;Rajita Sinha;Dimitri E Grigoriadis;Emilio Merlo Pich;Lorenzo Leggio;Markus Heilig
  • 通讯作者:
    Markus Heilig

David T George的其他文献

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{{ truncateString('David T George', 18)}}的其他基金

Assessment,Treatment, and Pharmacological Interventions in Alcoholic Patients
酗酒患者的评估、治疗和药理学干预
  • 批准号:
    8156730
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
Characterization Of Perpetrators Of Domestic Violence
家庭暴力施暴者的特征
  • 批准号:
    7146174
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
Clinical trial of SR141716, Rimonabant, to reduce volunt
SR141716、利莫那班的临床试验,以减少自愿
  • 批准号:
    6983095
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
Characterization Of Perpetrators Of Domestic Violence
家庭暴力施暴者的特征
  • 批准号:
    6983065
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
Clinical Studies Investigating Aggressive Behaviors And
调查攻击行为和
  • 批准号:
    6983107
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
Clinical Studies Investigating Aggressive Behaviors And
调查攻击行为和
  • 批准号:
    7317742
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
Characterization of Perpetrators of Domestic Violence
家庭暴力施暴者的特征
  • 批准号:
    6431370
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
YOHIMBINE CHALLENGE TO STUDY NORADRENERGIC FUNCTION IN INDIVIDUALS
育亨宾挑战研究个体去甲肾上腺素能功能
  • 批准号:
    6097574
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
Clinical Assessment and Treatment Evaluation of Alcohol Dependent Patients
酒精依赖患者的临床评估和治疗评价
  • 批准号:
    7963833
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:
SR141716, Rimonabant, to reduce alcohol consumption
SR141716,利莫那班,减少酒精消耗
  • 批准号:
    7146650
  • 财政年份:
  • 资助金额:
    $ 17.28万
  • 项目类别:

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