In vitro and in vivo inhibition of rat liver aldehyde dehydrogenase by S-methyl N,N-diethylthiolcarbamate sulfoxide, a new metabolite of disulfiram.
In summary, these data provide the first evidence that DETC-MeSO is a natural metabolite of disulfiram, and a potent inhibitor of rat liver mitochondrial low Km ALDH both in vitro and in vivo. It is therefore proposed that, based upon evidence to date, DETC-MeSO appears to be the chemical species to which disulfiram must be bioactivated, and is the metabolite most likely responsible for disulfiram's inhibition of rat liver mitochondrial low Km ALDH in vivo. Characterization of the properties of DETC-MeSO as the metabolite responsible for disulfiram's action as an ALDH inhibitor is presently in the process of being completed.
Hart
B W
BW
Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045.
Faiman
M D
MD
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D004221:Disulfiram / Q000378:metabolism*; D004050:Ditiocarb / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats
C073220:S-methyl N,N-diethylthiolcarbamate sulfoxide; D004050:Ditiocarb; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram