Abstract
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 (< 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.
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