地西泮对脑内S-腺苷-L-甲硫氨酸和S-腺苷-L-高半胱氨酸水平的影响：与对甲硫氨酸亚砜亚胺诱发癫痫的保护作用可能存在的相关性。

The effect of diazepam on brain levels of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine: possible correlation with protection from methionine sulfoximine seizures.

作者信息

Gill M W, Schatz R A

出版信息

Res Commun Chem Pathol Pharmacol. 1985 Dec;50(3):349-63.

Abstract

Administration of the long latency convulsant, L-methionine-d,1-sulfoximine (MSO) results in an increase in brain methylation flux. We determined the effects of the anticonvulsant, diazepam (DZ) on MSO seizures and on brain levels of S-adenosyl-L-methionine (AdoMet) and S-adenosyl-L-homocysteine (AdoHcy) to indicate possible alterations in the brain methylation pathway. We report a dose related inhibition of MSO seizures by DZ. In addition, DZ significantly increased brain levels of AdoMet and AdoHcy and reversed the MSO-induced decreases in AdoMet and AdoHcy. DZ also blocked the MSO induced increase in the methylation index (AdoMet/AdoHcy). The data indicates an inhibition of MSO induced increases in brain methylation by DZ. Possible mechanisms for the effect of DZ on the cerebral methylation pathway are discussed.

摘要

给予长潜伏期惊厥剂L-蛋氨酸-d，1-亚砜亚胺（MSO）会导致脑甲基化通量增加。我们确定了抗惊厥药地西泮（DZ）对MSO诱发的癫痫发作以及对脑内S-腺苷-L-甲硫氨酸（AdoMet）和S-腺苷-L-高半胱氨酸（AdoHcy）水平的影响，以表明脑甲基化途径可能发生的改变。我们报告了DZ对MSO诱发癫痫发作的剂量相关抑制作用。此外，DZ显著提高了脑内AdoMet和AdoHcy的水平，并逆转了MSO引起的AdoMet和AdoHcy的降低。DZ还阻断了MSO诱导的甲基化指数（AdoMet/AdoHcy）升高。数据表明DZ抑制了MSO诱导的脑甲基化增加。文中讨论了DZ对脑甲基化途径产生作用的可能机制。