Lingham T, Perlanski E, Grupp L A
Department of Pharmacology, University of Toronto, Ontario, Canada.
Alcohol Clin Exp Res. 1990 Feb;14(1):92-9. doi: 10.1111/j.1530-0277.1990.tb00453.x.
Alcoholism is a prevalent problem of contemporary society, yet there are virtually no clinically effective drugs for the management of this disorder. A previous study demonstrating the ability of angiotensin-converting enzyme (ACE) inhibitors to attenuate voluntary alcohol intake in rats prompted the suggestion that these drugs, currently marketed for the treatment of hypertension, may also be useful in dealing with human alcohol abuse. The present experiments explored in more detail the effect and possible mechanisms of action of this class of drug on alcohol consumption in rats. Experiment one demonstrated that Abutapril, a new ACE inhibitor, significantly reduced alcohol intake and that this effect could not be blocked by either an ANG II or an opiate receptor antagonist suggesting that neither the peripheral renin-angiotensin system (RAS) nor the endogenous enkephalins are involved in the ability of ACE inhibition to attenuate alcohol intake. Experiments two and three showed that ACE inhibition effectively reduced alcohol drinking faster in animals with elevated RAS activity and not at all in animals with suppressed RAS activity indicating that initial levels of RAS activity may determine the speed and ability of ACE inhibition to attenuate alcohol intake. ACE inhibitors may reduce alcohol intake by elevating a nonapeptide fragment or by elevating central ANG II levels. The assessment of this class of drugs to reduce alcohol intake in humans should include a monitoring of the initial level of activity in the renin-angiotensin system since this may be a predictor of the effectiveness of treatment with the ACE inhibitors.
酒精成瘾是当代社会一个普遍存在的问题，然而实际上尚无临床上有效的药物来治疗这种疾病。先前有一项研究表明血管紧张素转换酶（ACE）抑制剂能够减少大鼠的自愿饮酒量，这促使人们提出，这类目前用于治疗高血压的药物，或许也可用于治疗人类的酒精滥用问题。本实验更详细地探究了这类药物对大鼠酒精摄入量的影响及其可能的作用机制。实验一表明，新型ACE抑制剂阿替普利能显著减少酒精摄入量，且这种作用既不能被血管紧张素II（ANG II）拮抗剂也不能被阿片受体拮抗剂阻断，这表明外周肾素 - 血管紧张素系统（RAS）和内源性脑啡肽均不参与ACE抑制作用减少酒精摄入量的过程。实验二和实验三表明，ACE抑制作用能更有效地降低RAS活性升高的动物的酒精饮用量，而对RAS活性受到抑制的动物则完全没有作用，这表明RAS活性的初始水平可能决定了ACE抑制作用减少酒精摄入量的速度和能力。ACE抑制剂可能通过升高一种九肽片段或升高中枢ANG II水平来减少酒精摄入量。对这类药物减少人类酒精摄入量的评估应包括监测肾素 - 血管紧张素系统的初始活性水平，因为这可能是ACE抑制剂治疗效果的一个预测指标。
