Sulfiram, a
drug applied topically to treat
scabies, produces effects similar to those of
disulfiram after subsequent ingestion of
ethanol.
Disulfiram, used in aversion therapy in the treatment of
alcoholism, inhibits hepatic
aldehyde dehydrogenase (ALDH) causing an accumulation of
acetaldehyde after
ethanol ingestion. The increased tissue levels of
acetaldehyde cause a spectrum of undesirable side-effects including
flushing,
nausea,
vomiting, and
tachycardia, which are referred to as the
disulfiram reaction. Previous studies have shown that in vitro
sulfiram is a very weak inhibitor of ALDH, but solutions of
sulfiram markedly increase in potency with time. In the present study, fresh solutions of
sulfiram were exposed to fluorescent room light under ambient conditions and analyzed at timed intervals by HPLC. At least eight products, including
disulfiram, were formed in the light-exposed
sulfiram solutions, but not in solutions kept in the dark. Structural characterization of two of the photolysis products was obtained by on-line microbore HPLC-mass spectrometry (mu LC-MS) and on-line microbore HPLC-tandem mass spectrometry (mu LC-MS/MS) using continuous flow-liquid secondary ion mass spectrometry (CF-LSIMS) as the primary ionization method.
Sulfiram was converted to
disulfiram at an initial rate of 0.7%/hr, and the formation of
disulfiram correlated with the increase in ALDH inhibition in vitro. The results of this investigation show that while
sulfiram is a weak inhibitor of ALDH in vitro, it is readily photoconverted to
disulfiram, a very potent inhibitor of ALDH, which may explain the adverse reaction to
ethanol after
sulfiram therapy.