S-methyl N,N-diethylthiolcarbamate sulfone, an in vitro and in vivo inhibitor of rat liver mitochondrial low Km aldehyde dehydrogenase

Biochem Pharmacol. 1994 Apr 20;47(8):1465-7. doi: 10.1016/0006-2952(94)90350-6.

Abstract

S-Methyl N,N-diethylthiolcarbamate sulfone (DETC-Me sulfone) was investigated for its rat liver mitochondrial low Km aldehyde dehydrogenase (ALDH2) inhibitory properties. DETC-Me sulfone inhibited ALDH2 in vitro (IC50 = 3.8 microM) and in vivo (ID50 = 170 mumol/kg; 31 mg/kg). Maximum inhibition (60%) of ALDH2 was observed 8 hr after DETC-Me sulfone administration. In addition, incubation of S-methyl N,N-diethylthiolcarbamate (DETC-Me) or S-methyl N,N-diethylthiolcarbamate sulfoxide (DETC-Me sulfoxide) with rat liver microsomes and an NADPH-generating system failed to produce DETC-Me sulfone. Furthermore, DETC-Me sulfone could not be detected in plasma from rats treated with either DETC-Me sulfoxide or DETC-Me sulfone. In conclusion, DETC-Me sulfone inhibited ALDH2 in vitro and in vivo. However, there was no evidence suggesting that DETC-Me sulfoxide was metabolized to DETC-Me sulfone.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehyde Dehydrogenase / antagonists & inhibitors*
  • Animals
  • Disulfiram / metabolism
  • Ditiocarb / analogs & derivatives*
  • Ditiocarb / chemical synthesis
  • Ditiocarb / metabolism
  • Ditiocarb / pharmacology
  • Male
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / enzymology
  • Oxidation-Reduction
  • Rats
  • Thiocarbamates / metabolism

Substances

  • S-methyl-N,N-diethylthiolcarbamate sulfone
  • Thiocarbamates
  • S-methyl N,N-diethylthiolcarbamate sulfoxide
  • S-methyl diethylthiocarbamate
  • Ditiocarb
  • Aldehyde Dehydrogenase
  • Disulfiram