DAIDZIN AND DAIDZEIN SUPPRESS FREE-CHOICE ETHANOL INTAKE BY SYRIAN GOLDEN-HAMSTERS

DAIDZIN AND DAIDZEIN SUPPRESS FREE-CHOICE ETHANOL INTAKE BY SYRIAN GOLDEN-HAMSTERS
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DOI:
10.1073/pnas.90.21.10008
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发表时间:
1993-11-01
影响因子:
11.1
通讯作者:
VALLEE, BL
VALLEE, BL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KEUNG, WM;VALLEE, BL

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叙利亚金仓鼠在简单的两瓶自由选择方案中更喜欢并消耗大量且非常恒定的乙醇。齐美利定、溴隐碱、丁螺环酮和碳酸锂可显著抑制乙醇摄入,这些药物已被证明对酒精依赖者控制乙醇摄入有益。这些结果表明,这种酒精饮用动物模型具有很高的“预测效度”,可以有效地用于寻找和鉴定治疗酒精滥用的新药物。该模型使我们能够证实假定的葛根(RP)的抗斜视作用,这种草药长期用于治疗滥用酒精的患者。RP粗提取物,剂量为1.5 g.kg-1。第1天显著抑制了金仓鼠自由选择乙醇的摄入量(约50%)。此外,RP的两种主要成分大豆苷元(4′,7-二羟基异黄酮)和大豆苷元(大豆苷元的7-葡萄糖苷)也被证明可以抑制自由选择乙醇的摄入。大豆苷元和大豆苷元,剂量分别为150毫克和230毫克。第1天,分别抑制乙醇摄入量50%。RP、大豆黄素和大豆黄素处理对仓鼠的体重和水或食物摄入量没有显著影响。这些发现确定了一类化合物,有望作为安全有效的酒精滥用治疗剂。
Syrian Golden hamsters prefer and consume large and remarkably constant amounts of ethanol in a simple two-bottle free-choice regimen. Ethanol intake is significantly suppressed by zimelidine, bromocryptine, buspirone, and lithium carbonate, pharmacological agents that have been shown to be beneficial in controlling ethanol intake in alcohol-dependent humans. These results suggest that this ethanol-drinking animal model has high ''predictive validity'' and can be used effectively in the search for and identification of new agents for the treatment of alcohol abuse. The model has enabled us to confirm the putative antidipsotropic effect of Radix puerariae (RP), an herb long used in traditional Chinese medicine for the treatment of patients who abuse alcohol. A crude extract of RP at a dose of 1.5 g.kg-1.day-1 significantly suppresses (>50%) the free-choice ethanol intake of Golden hamsters. Moreover, two major constituents of RP, daidzein (4',7-dihydroxyisoflavone) and daidzin (the 7-glucoside of daidzein), were also shown to suppress free-choice ethanol intake. Daidzin and daidzein, at doses of 150 and 230 mg.kg-1.day-1, respectively, suppress ethanol intake by >50%. RP, daidzein, and daidzin treatment do not significantly affect the body weight and water or food intake of the hamsters. These findings identify a class of compounds that offer promise as safe and effective therapeutic agents for alcohol abuse.