Petersen E N
Department of Pharmacology, A/S Dumex, Copenhagen S, Denmark.
Eur J Pharmacol. 1989 Aug 3;166(3):419-25. doi: 10.1016/0014-2999(89)90354-3.
A recently discovered metabolite, diethylthiocarbamic acid methyl ester (Me-DTC), has been found in the plasma of man and rats in much higher concentrations than any other described metabolite after therapeutic doses of disulfiram. Me-DTC, in contrast to other disulfiram metabolites, is a potent inhibitor of liver aldehyde dehydrogenase (ALDH) in vitro. Like disulfiram, Me-DTC had a pronounced hypothermic effect in rats. This hypothermic effect and the augmented blood pressure response to ethanol challenge in rats developed rapidly with Me-DTC but were somewhat delayed with disulfiram. The blood pressure response outlasted the presence of Me-DTC in plasma (less than 24 h); a significant effect was found 48 h after pretreatment but not 72 h after a single dose. No effect was observed when ethanol was given 15 min before Me-DTC or disulfiram. These latter two observations are consistent with a function of Me-DTC as a suicide inhibitor of ALDH. Since Me-DTC has been reported to inhibit ALDH in vitro, even under anaerobic conditions, Me-DTC may be the active metabolite of disulfiram.
最近发现的一种代谢产物，二乙基硫代氨基甲酸甲酯（Me-DTC），在人和大鼠血浆中被发现，其浓度比治疗剂量的双硫仑后的任何其他已描述代谢产物都高得多。与其他双硫仑代谢产物不同，Me-DTC在体外是肝脏醛脱氢酶（ALDH）的有效抑制剂。与双硫仑一样，Me-DTC在大鼠中具有明显的体温过低效应。这种体温过低效应以及大鼠对乙醇激发的血压反应增强，Me-DTC时迅速出现，但双硫仑时则有所延迟。血压反应在血浆中Me-DTC存在后持续存在（不到24小时）；预处理后48小时发现有显著作用，但单次给药后72小时未发现。在Me-DTC或双硫仑前15分钟给予乙醇时未观察到作用。后两个观察结果与Me-DTC作为ALDH自杀性抑制剂的功能一致。由于据报道Me-DTC即使在厌氧条件下在体外也能抑制ALDH，Me-DTC可能是双硫仑的活性代谢产物。
