Spinosa G, Perlanski E, Leenen F H, Stewart R B, Grupp L A
Department of Pharmacology, University of Toronto, Canada.
Alcohol Clin Exp Res. 1988 Feb;12(1):65-70. doi: 10.1111/j.1530-0277.1988.tb00134.x.
The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.
重度饮酒的流行率在全球范围内是一个比例不断增加的主要问题。尽管酒精增敏药物以及最近的血清素摄取抑制剂是有一些追随者的药物干预措施,但其长期有益效果尚未得到证实。近年来,我们已经证明,操纵肾素 - 血管紧张素系统的活性会显著改变大鼠的自愿饮酒量。基于这些发现,本研究评估了一类被称为血管紧张素转换酶抑制剂的药物在实验动物中减少自愿饮酒的能力。这些药物可防止血管紧张素I转化为血管紧张素II。它们已在欧洲和北美获得许可使用,并被用于治疗高血压。我们的实验表明,卡托普利(开博通,施贵宝公司)和依那普利(悦宁定,默克夏普&多贺美公司)都可以减少正常血压和高血压动物的饮酒量,无论摄入模式是一次性大量饮酒还是不那么夸张的饮酒方式。此外,饮酒量的这种变化可以在血压、血浆肾素活性、总体液体平衡或酒精的分布和代谢没有伴随变化的情况下发生。综合这些发现表明,血管紧张素转换酶抑制剂应该在临床环境中进行评估,因为它们可能被证明是一种对人类酒精滥用有用的新治疗方法或治疗辅助手段。