Modulation of ethanol intake by serotonin uptake inhibitors.
Modulation of ethanol intake by serotonin uptake inhibitors.
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通过血清素摄取抑制剂调节乙醇摄入量。
DOI：
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发表时间：
1986
影响因子：
5.3
通讯作者：
Lawrin Mo
中科院分区：
文献类型：
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作者：
Claudio A. Naranjo;Edward M. Sellers;Lawrin Mo
最常见的减少酒精摄入量的处方药是酒精敏感剂；然而，它们的有效性尚未得到证实，它们与毒性有关，而且有几个使用禁忌症。一项旨在识别和测试减少酒精摄入量的新药的计划，重点放在了增强中枢5-羟色胺能神经传递并持续减少酒精摄入量的药物上。动物研究表明，直接和间接5-羟色胺(5-HT)激动剂的结果是一致的。在给予5-羟色胺前体、5-羟色胺摄取抑制剂、脑内5-羟色胺和突触后5-羟色胺激动剂后，乙醇摄入量减少；相反，用5，6-或5，7-二羟色胺破坏含5-羟色胺的神经元后，酒精摄入量增加。口服齐美利定(200 mg/d)到16个健康的酒精滥用者与戒酒天数显著增加和饮酒量减少有关。约50%的受试者为应答者，35%为部分应答者，10%-15%为无应答者。在最近的一项双盲交叉研究中，西酞普兰，一种更具选择性的5-羟色胺吸收抑制剂，产生了类似的结果。由于5-羟色胺摄取抑制剂起效快，而且受试者在临床上没有抑郁，这种作用有别于抗抑郁作用。这些药物很可能会干扰调节酒精摄入量的神经生物机制，并为调节问题饮酒者的酒精使用提供了一种创新的方法。
The most commonly prescribed agents for decreasing ethanol intake are alcohol-sensitizing drugs; however, their efficacy is unproven, they are associated with toxicity, and there are several contraindications for use. A program to identify and test new drugs to decrease ethanol intake has focused on drugs that enhance central serotonergic neurotransmission and consistently attenuate ethanol consumption. Animal studies have shown consistent findings with direct and indirect serotonin (5-HT) agonists. Ethanol intake decreased after the administration of 5-HT precursors, 5-HT uptake inhibitors, intracerebral 5-HT, and postsynaptic 5-HT agonists; in contrast, destruction of serotonin-containing neurons with 5,6- or 5,7-dihydroxytryptamine increased ethanol intake. Administration of zimelidine (200 mg/day p.o.) to 16 healthy alcohol abusers was associated with a significant increase in number of abstinent days and a decrease in number of drinks consumed. Approximately 50% of the subjects were responders, 35% were partial responders, and 10%-15% were nonresponders. In a recent double-blind crossover study, citalopram, an even more selective serotonin uptake inhibitor, produced similar results. Because serotonin uptake inhibitors acted rapidly and subjects were not clinically depressed, this action is distinct from antidepressant effects. These drugs most likely interfere with the neurobiologic mechanisms regulating ethanol intake and provide an innovative approach for modulating the use of alcohol in problem drinkers.