Smith A A
Adv Exp Med Biol. 1975;56:265-75. doi: 10.1007/978-1-4684-7529-6_13.
Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.
乙醇通过其主要代谢产物乙醛竞争性抑制醛脱氢酶底物的氧化。结果，生物胺形成了更多量的醇类而非相应的酸类。在这种生物转化过程中，脱氨基胺与完整胺之间可能会发生缩合反应，从而产生四氢罂粟啉。这些化合物与阿片类药物的前体密切相关，这就是将乙醇滥用与吗啡成瘾联系起来的原因。然而，没有药理学或临床证据表明乙醇依赖或阿片类成瘾之间存在相似性。乙醛在体外生物碱形成过程中还起着额外作用。生物胺可能与乙醛反应形成异喹啉或咔啉化合物。其中一些物质具有显著的药理活性。此外，它们可能进入神经储存部位并取代天然神经递质。因此，它们可以充当假神经递质。一些研究人员认为，长期摄入乙醇会导致大量此类异常化合物的形成，进而可能扰乱自主神经系统平衡。这种紊乱可能解释了戒断时出现的异常交感神经活动。虽然这些关于酒精滥用病因的观点具有一定吸引力，但它们自然是基于体外初步研究。在对这些化合物在动物体内的定量药理学进行大量研究之前，无法对所提出假设的价值做出判断。与此同时，对乙醇抑制小鼠呼吸能力的药理学研究表明，与阿片类药物或巴比妥类药物不同，乙醇诱导的呼吸抑制需要大脑中存在血清素。这种神经递质也介导其他几种醇类的呼吸作用，但奇怪的是，不介导水合氯醛的呼吸作用，然而据称这种化合物与乙醇一样会改变生物胺代谢。因此，通过呼吸抑制作用，乙醇的反应在药理学上可以与其他主要麻醉品类如阿片类药物和巴比妥类药物区分开来。乙醇和其他几种醇类对血清素介导的特定需求为酒精滥用的合理治疗方法打开了大门。与此同时，这一发现往往降低了酗酒在某种程度上与成瘾性生物碱形成有关的可能性。
