Effects of metyrapone on liver microsomal drug oxidations.
Effects of metyrapone on liver microsomal drug oxidations.
复制标题
美替拉酮对肝微粒体药物氧化的影响。
DOI：
10.1016/s0021-9258(19)70262-2
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发表时间：
1969
影响因子：
3.6
通讯作者：
K. Leibman
中科院分区：
文献类型：
--
作者：
K. Leibman
Metyrapone [2-methyl-1,2-bis(3-pyridyl)-1-propanone], an inhibitor of adrenal steroid hydroxylation, has been shown to affect a number of liver microsomal drug-oxidizing enzyme systems. The metabolism of hexobarbital and that of aminopyrine are inhibited in vitro by this drug in microsomal preparations from control and phenobarbital-treated rats. Hexobarbital sleeping time is prolonged by metyrapone in both groups of rats. Demethylation of morphine and hydroxylation of tyramine are inhibited to a lesser extent, and NADPH oxidase is little affected. In contrast, the effect of metyrapone on the formation of phenolic metabolites from acetanilide follows a biphasic relationship with respect to metyrapone concentration: inhibition occurs only at very high concentrations, and the reaction is greatly enhanced at lower concentrations with both control and phenobarbital-induced preparations. Trichloroethylene oxidation is also enhanced by metyrapone in both preparations, but the enhancement in phenobarbital-induced preparations is superimposed on an inhibitory effect. Studies with the latter pathway show that both effects are independent of the NADPH-generating system, and are exerted in a reversible manner.
