Dutasteride reduces alcohol's sedative effects in men in a human laboratory setting and reduces drinking in the natural environment.
Dutasteride reduces alcohol's sedative effects in men in a human laboratory setting and reduces drinking in the natural environment.
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DOI：
10.1007/s00213-014-3487-4
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Kranzler, Henry R.
中科院分区：
文献类型：
--
作者：
Covault, Jonathan;Pond, Timothy;Feinn, Richard;Arias, Albert J.;Oncken, Cheryl;Kranzler, Henry R.
临床前研究支持内源性神经活性类固醇介导酒精某些作用的假设。本研究的目的是研究杜他雄胺抑制5α-减少的神经活性类固醇生成对成年男性酒精主观反应的影响。使用受试者内因子设计，70名男性完成了4个随机顺序的每月疗程，其中预处理为4mg度他雄胺或安慰剂，同时搭配中等剂量的酒精（0.8 g/kg）或安慰剂饮料。杜他雄胺的药理作用是通过测定血清雄甾二醇葡萄糖醛酸盐来测定的。使用双相酒精效应量表（BAES）和酒精感觉量表（SS），每隔40分钟获得酒精效应的自我报告。我们使用线性混合模型来检验杜他雄胺和酒精对BAES和SS反应的影响，以及杜他雄胺与GABRA2酒精依赖相关多态性rs279858的相互作用。我们还检查了在每次实验后的几周内暴露于杜他雄胺是否会影响饮酒。单次4毫克剂量的杜他雄胺可使雄甾二醇葡萄糖醛酸酯减少70%。杜他雄胺预处理降低了酒精对BAES镇静和SS麻醉的影响。杜他雄胺与rs279858无相互作用。重度饮酒者在杜他雄胺治疗后的两周内，重度饮酒天数减少，在杜他雄胺治疗后的第一周内，总饮酒量减少。这些结果证明，神经活性类固醇介导了酒精对成年男性的一些镇静作用，而度他雄胺可能通过其对神经活性类固醇浓度的影响而减少饮酒量。
Preclinical studies support the hypothesis that endogenous neuroactive steroids mediate some effects of alcohol. The aim of this study was to examine the effect of dutasteride inhibition of 5α-reduced neuroactive steroid production on subjective responses to alcohol in adult men. Using a within-subject factorial design, 70 men completed four randomly ordered monthly sessions in which pretreatment with 4 mg dutasteride or placebo was paired with a moderate dose of alcohol (0.8 g/kg) or placebo beverage. The pharmacologic effect of dutasteride was measured by an assay of serum androstanediol glucuronide. Self-reports of alcohol effects were obtained at 40-min intervals following alcohol administration using the Biphasic Alcohol Effects Scale (BAES) and the Alcohol Sensation Scale (SS). We used linear mixed models to examine the effects of dutasteride and alcohol on BAES and SS responses and the interaction of dutasteride with the GABRA2 alcohol dependence-associated polymorphism rs279858. We also examined whether exposure to dutasteride influenced drinking in the weeks following each laboratory session. A single 4-mg dose of dutasteride produced a 70 % reduction in androstanediol glucuronide. Dutasteride pretreatment reduced alcohol effects on the BAES sedation and SS anesthesia scales. There was no interaction of dutasteride with rs279858. Heavy drinkers had fewer heavy drinking days during the 2 weeks following the dutasteride sessions and fewer total drinks in the first week after dutasteride. These results provide evidence that neuroactive steroids mediate some of the sedative effects of alcohol in adult men and that dutasteride may reduce drinking, presumably through its effects on neuroactive steroid concentrations.
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影响因子：
4.1
作者：
MAISTO, SA;CONNORS, GJ;ADESSO, VJ
通讯作者：
ADESSO, VJ
DOI：
10.1016/0022-4731(85)90147-5
发表时间：
1985-01-01
影响因子：
4.1
作者：
HOLZBAUER, M;BIRMINGHAM, MK;OLIVERS, JT
通讯作者：
OLIVERS, JT
影响因子：
2.9
作者：
BITRAN, D;HILVERS, RJ;KELLOGG, CK
通讯作者：
KELLOGG, CK
影响因子：
56.9
作者：
MAJEWSKA, MD;HARRISON, NL;PAUL, SM
通讯作者：
PAUL, SM
影响因子：
2.7
作者：
Frye, CA;VanKeuren, KR;Erskine, MS
通讯作者：
Erskine, MS