The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder.
The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder.
复制标题
DOI：
10.1007/s00213-020-05599-5
复制
发表时间：
2020-10
影响因子：
3.4
通讯作者：
Mitchell JM
中科院分区：
文献类型：
--
作者：
Coker AR;Weinstein DN;Vega TA;Miller CS;Kayser AS;Mitchell JM
患有酒精使用障碍（AUD）的个体表现出决策困难和冲动，这可能与额叶皮质功能受损有关。增强额叶多巴胺张力的治疗方法可以降低冲动性，从而减少AUD患者的饮酒量。确定儿茶酚-O-甲基转移酶（COMT）抑制剂托卡朋是否可以减少AUD患者的饮酒量，以及这种减少是否与托卡朋诱导的实验室决策任务变化相关。我们使用每日自我报告和一种新的小组实验室酒吧任务，以评估随机双盲交叉给予托卡朋（100 mg TID 5天）对55名非寻求治疗的AUD受试者的饮酒量和实验室任务评估冲动的影响。托卡朋显著降低自我报告的饮酒量（t（54）= 2.05，p = 0.045）。托卡朋对饮酒的影响与冲动决策的变化显著相关，因此，对托卡朋的冲动选择减少最多的受试者也报告了饮酒量的最大减少（r（45）= 0.40，p = 0.0053）。我们没有看到托卡朋对实验室酒吧消费的影响。不良事件（AE）报告率较低，托卡朋与安慰剂组AE的频率或严重程度无显著差异。这些数据表明，COMT抑制剂如托卡朋可能是AUD的有用治疗剂。
Individuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD. To determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory based decision-making tasks. We used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100 mg TID for 5 days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment seeking subjects with AUD. Tolcapone significantly reduced self-reported alcohol consumption (t(54) = 2.05, p = 0.045). The effects of tolcapone on drinking significantly correlated with changes in impulsive decision-making, such that subjects with the greatest decrease in impulsive choice on tolcapone also reported the greatest decrease in alcohol consumption (r(45) = 0.40, p = 0.0053). We did not see effects of tolcapone on laboratory bar consumption. Adverse event (AE) reporting was low, with no significant difference in frequency or severity of AEs on tolcapone versus placebo. These data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD.
登录
查看更多内容
影响因子：
5.3
作者：
Sheehan, DV;Lecrubier, Y;Dunbar, GC
通讯作者：
Dunbar, GC
影响因子：
5.3
作者：
Boettiger, Charlotte A.;Mitchell, Jennifer M.;Fields, Howard L.
通讯作者：
Fields, Howard L.
影响因子：
6.7
作者：
Jorga, KM;Kroodsma, JM;van Hattum, J
通讯作者：
van Hattum, J
DOI：
10.1038/tpj.2016.43
发表时间：
2016-10
期刊：
The pharmacogenomics journal
影响因子：
--
作者：
Schacht JP
通讯作者：
Schacht JP
影响因子：
4.7
作者：
Bickel WK;Koffarnus MN;Moody L;Wilson AG
通讯作者：
Wilson AG