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优降宁和其他单胺氧化酶抑制剂对乙醇中毒小鼠血液乙醛水平的影响。

The effect of pargyline and other monoamine oxidase inhibitors on blood acetaldehyde levels in ethanol-intoxicated mice.

作者信息

Dembiec D, MacNamee D, Cohen G

出版信息

J Pharmacol Exp Ther. 1976 May;197(2):332-9.

PMID:944772
Abstract

Pargyline (100 mg/kg i.p.) administered to Swiss-Webster mice prior to the injection of ethanol (4 g/kg i.p.) elevated blood acetaldehyde levels to a mean of 20 mug/ml, compared to less than 1 mug/ml in control mice treated with ethanol alone. Elevated blood acetaldehyde was observed when ethanol was given at 15 minutes, 2 or 5 hours after pargyline; the action of pargyline had largely disappeared after 18 hours. The magnitude of the increase in blood acetaldehyde levels was dependent upon the dose of pargyline between 20 and 100 mg/kg; however, the elevation was relatively independent of the ethanol dose between 1 and 6 g/kg. Of the other monoamine oxidase inhibitors tested, Lilly 51641 showed a strong elevation in acetaldehyde (mean 13.3 mug/ml), whereas deprenyl and clorgyline gave modest elevations (2.9 and 2.6 mug/ml, respectively), and nialamide and tranylcypromine were only weakly active (1.4 and 1.2 mug/ml, respectively). Blood acetaldehyde levels in mice treated with pargyline and ethanol were strongly depressed (85%) by pyrazole, an inhibitor of alcohol dehydrogenase, and moderately to strongly depressed (49-71%) by pretreatment with phenobarbital, an inducer of liver aldehyde dehydrogenase.

摘要

在给瑞士-韦伯斯特小鼠腹腔注射乙醇(4克/千克)之前,先腹腔注射优降宁(100毫克/千克),与仅用乙醇处理的对照小鼠相比,血液乙醛水平升高至平均20微克/毫升,而对照小鼠的该水平低于1微克/毫升。当在优降宁注射后15分钟、2小时或5小时给予乙醇时,观察到血液乙醛水平升高;优降宁的作用在18小时后基本消失。血液乙醛水平升高的幅度取决于优降宁的剂量,范围在20至100毫克/千克之间;然而,这种升高相对独立于1至6克/千克之间的乙醇剂量。在所测试的其他单胺氧化酶抑制剂中,礼来51641使乙醛水平大幅升高(平均13.3微克/毫升),而司来吉兰和氯吉兰使乙醛水平有适度升高(分别为2.9和2.6微克/毫升),尼亚酰胺和反苯环丙胺的活性较弱(分别为1.4和1.2微克/毫升)。用优降宁和乙醇处理的小鼠的血液乙醛水平被酒精脱氢酶抑制剂吡唑强烈抑制(85%),并被肝醛脱氢酶诱导剂苯巴比妥预处理适度至强烈抑制(49 - 71%)。

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