S-METHYL-N,N-DIETHYLTHIOLCARBAMATE - A DISULFIRAM METABOLITE AND POTENT RAT-LIVER MITOCHONDRIAL LOW KM ALDEHYDE DEHYDROGENASE INHIBITOR

被引：30

作者：

HART, BW ^{[1
]}

YOURICK, JJ ^{[1
]}

FAIMAN, MD ^{[1
]}

机构：

[1] UNIV KANSAS,DEPT PHARMACOL & TOXICOL,LAWRENCE,KS 66045

来源：

ALCOHOL | 1990年 / 7卷 / 02期

关键词：

Aldehyde dehydrogenase inhibition; DETC-Me; Disulfiram metabolites;

D O I：

10.1016/0741-8329(90)90079-R

中图分类号：

R194 [卫生标准、卫生检查、医药管理];

学科分类号：

摘要：

S-methyl-N,N-diethylthiolcarbamate-methyl ester (DETC-Me), a proposed disulfiram metabolite, was investigated both in vivo and in vitro for its effectiveness as a liver mitochondrial low Km aldehyde dehydrogenase (L Km ALDH) inhibitor. Male Sprague-Dawley rats were treated intraperitoneally with DETC-Me, killed at various times and L Km ALDH determined. DETC-Me was found to be a more potent in vivo inhibitor of L Km ALDH than either disulfiram, diethyldithiocarbamate (DDTC) or diethyldithiocarbamate-methyl ester (DDTC-Me). The ID50 for DETC-Me, DDTC-Me and disulfiram was 6.5, 15.5 and 56.2 mg/kg, respectively. The ID50 for DDTC was similar to DDTC-Me. Maximal inhibition of L Km ALDH occurred 30 minutes after DETC-Me administration. DETC-Me was ineffective as an in vitro inhibitor. DETC-Me produced a marked disulfiram-ethanol reaction (DER) at one-quarter of the dose of disulfiram or DDTC. Plasma DETC-Me in rats was greater after DETC-Me administration than after DDTC-Me, DDTC or disulfiram. In conclusion, DETC-Me is proposed to be a metabolite of disulfiram, and may be the immediate precursor of the chemical species responsible for L Km ALDH inhibition. © 1990.

引用

页码：165 / 169

页数：5

共 22 条

[1] HOW EFFECTIVE IS THE STANDARD DOSE OF DISULFIRAM - A REVIEW OF THE ALCOHOL-DISULFIRAM REACTION IN PRACTICE [J].