Studies on the cyanamide-ethanol interaction. Dimethylcyanamide as an inhibitor of aldehyde dehydrogenase in vivo.
Studies on the cyanamide-ethanol interaction. Dimethylcyanamide as an inhibitor of aldehyde dehydrogenase in vivo.
复制标题
氰胺-乙醇相互作用的研究。
DOI：
10.1016/0006-2952(82)90412-9
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发表时间：
1982
影响因子：
5.8
通讯作者：
H. Nagasawa
中科院分区：
文献类型：
--
作者：
F. Shirota;E. Demaster;H. Nagasawa
二甲基氰胺（DMC）给药后12-24小时，引起乙醇引起的血液乙醛（AcH）明显升高，并使线粒体醛脱氢酶（AlDH）的比活性降低90%。DMC和氰胺在升高血中乙酰胆碱的相对疗效的比较，分别在2小时和1小时后的药物治疗，表明DMC是至少五分之一的活性作为氰胺。然而，由于没有在DMC的最佳时间（12 - 24小时）进行比较，因此其体内活性可能接近氰胺本身。DMC在体外对大鼠肝线粒体中的lowKmAlDH同工酶基本上无抑制作用。尽管DMC的N-去甲基化产物甲基氰胺太不稳定而不能制备用于本评价，但化学合成了高级单烷基氰胺，n-丙基氰胺，并在体外显示出良好的线粒体酶抑制剂。这些结果表明，DMC必须被N-脱甲基化之前被转化为一个活性物种，抑制AlDH活性。
Administration of dimethylcyanamide (DMC) to rats caused a marked elevation in ethanol-derived blood acetaldehyde (AcH) and depressed the specific activity of the lowKmmitochondrial aldehyde dehydrogenase (AlDH) by 90% at 12–24 hr, coincident with depletion of hepatic glutathione levels. Comparison of the relative efficacy of DMC and cyanamide in elevating blood AcH measured at 2hr and 1 hr post-drug treatment, respectively, indicated that DMC was at least one-fifth as active as cyanamide. However, since the comparison was not made at optimal times for DMC (12–24 hr), it is likely that its activityin vivoapproaches that of cyanamide itself. DMC was essentially inactivein vitroas an inhibitor of the lowKmAlDH isozyme in intact rat liver mitochondria. Although methylcyanamide, the product ofN-demethylation of DMC, was too unstable to be prepared for this evaluation, the higher monoalkyl cyanamide,n-propylcyanamide, was synthesized chemically and was shown to be a good inhibitor of the mitochondrial enzymein vitro. These results suggest that DMC must beN-demethylated before being converted to a reactive species that inhibits AlDH activity.