Involvement of beta-carbolines in the symptoms of alcohol withdrawal

乙醇的代谢物乙醛与色氨酸的缩合反应产物四氢-β-咔啉-3-羧酸可被认为是苯二氮类受体拮抗剂β-咔啉-3-羧酸盐的可能前体。以甜菜碱为原料，在氧化条件下与部分醛反应，合成了β-卡博林(去甲肾上腺素)和1-甲基-β-卡布林(哈曼)。众所周知，这些β-卡宾存在于单胺氧化酶和苯二氮卓类受体的结合中。在本研究中，采用了一种包括化学键合材料、高效液相色谱和荧光检测的纯化程序来定量测定四氢-β-卡宾。并建立了高效液相色谱和质谱学方法对其进行鉴定。在各种酒精饮料中都可以检测到诺哈曼和哈曼，尽管含量很少。在酿造的酒精酒中发现了中等含量的四氢-β-卡宾-3-羧酸，而蒸馏出的酒中含有较低浓度的四氢-β-卡宾-3-羧酸。用气相色谱法测定血液中乙醇和乙醛水平。酒精摄入增加了四氢-β-卡宾-3-羧酸的排泄，但血液乙醛与尿中四氢-β-卡宾的排泄没有明显的相关性。

Tetrahydro-beta-carboline-3-carboxylic acid, a condensation reaction product of acetaldehyde, a metabolite of alcohol, with tryptophan can be considered a probable precursor of the benzodiazepine receptor antagonist, beta-carboline-3-carboxylate. beta-Carboline (norharman) and 1-methyl-beta-carboline (harman) have been prepared by the reaction of trytophan with some aldehydes under an oxidative condition. It is well known that these beta-carbolines inhabit monoamine oxidase and benzodiazepine receptor binding.In the present study, a purification procedure, involving a chemically-bonded material followed by HPLC combined with fluorometric detection, was used for the quantitative determination of tetraphydro-beta-carbolines. An HPLC and mass spectrometry method was also developed for their identification. Norharman and harman in various alcoholic beverages could be detected, although the contents were very small. Moderate amounts of tetrahydro-beta-carboline-3-carboxylic acid were found in brewed alcoholic bevarage, however, distillled spilits contained low concentration.Next, Urinary excretions of tetrahydro-beta-carbolines were measured in man after administration of ethanol (0.4g/kg). Blood ethanol and acetaldehyde levels were determined by gas chromatography. Ethanol intake caused increased excretion of tetrahydro-beta-carboline-3-carboxylic acid, though there was no significant correlation between blood acetaldehyde and urinary excretion of tetrahydro-beta-carbolines.