Disulfiram disulfide

Disulfiram may be made by the reaction of diethyl amine with carbon disulfide in the presence of sodium hydroxide. The (CjHjljNCSSNa intermediate is oxidatively coupled using hydrogen peroxide to give disulfiram. 

Kane FJ Jr Carbon disulfide intoxication from overdosage of disulfiram. Am J Psychiatry 127 690-694, 1970... 

Disulfiram [bis(diethylthiocarbamoyl)disulfide] used in the treatment of alcoholism can be assayed directly by pulse polarography in an aliquot of a solution of a ground tablet dissolved in ethanol-acetate buffer (pH 4.5) [133]. A mechanism for the electrode process was proposed involving the reaction of the disulfiram with the mercury drop to form an insoluble mercuric salt, which then underwent reduction at the electrode surface. 

Disulfide Reduction. Some disulfides, such as the drug disulfiram (Antabuse), are reduced to their sulfhydryl constituents. Many of these reactions are three-step... 

Disulfiram (tetraethylthiuram disulfide bis(diethylcarbamoyl) disulfide) is a fungicide, an accelerator used in vulcanizing during the manufacture of rubber polymer, and a prescription drug (Antabuse) used as an alcohol deterrent (ref. 179) ... 

A number of disulfides are reduced in mammals to their sulfhydryl compounds. An example is disulfiram (Antabuse), a drug used for the treatment of alcoholism (Figure 10.9D). 

The neurotoxic effects of disulfiram have been compared with those of carbon disulfide, a disulfiram metabolite (9). The results suggested that carbon disulfide may be responsible for the behavioural and neurological adverse effects of disulfiram. If so, other toxic effects of carbon disulfide might follow administration of high doses of disulfiram, such as parkinsonism, psychotic behaviour, and encephalopathy. 

Rainey JM Jr. Disulfiram toxicity and carbon disulfide poisoning. Am J Psychiatry 1977 134(4) 371-8. 

The lability of the disulfide bridge is also shown in the metabolism of disulfides, in which the disulfide bond is reduced to the corresponding thiol.4 For example, disulfiram (87), a drug used in the treatment of alcoholism, is reduced in vivo to N,N-diethyldithiocarbamic acid (88), the biologically active metabolite (Scheme57). 

Disulfiram has multiple mechanisms of toxicity. Its most well-defined action is inhibition of aldehyde dehydrogenase, which thereby diminishes the breakdown of acetaldehyde. Accumulation of carbon disulfide, a disulfiram metabolite, as well as inhibition of dopamine-/f-hydroxylase has also been associated with its toxicity. 

Figure 17 Reduction reactions of sulfur-containing compounds, such as diallyl disulfide, disulfiram, and flosequinan.

Djuric D, Postic-Grujin A, Graovac-Leposavic L, et al. 1973. Antabuse as an indicator of human susceptibility to carbon disulfide Excretion of diethyldithiocarbamate sodium in the urine of workers exposed to CS2 after oral administration of disulfiram. Arch Environ Health 26 287-289. 

El-Hawari AM. 1978. Potentiation of dibromoethane (EDB) toxicity by disulfiram, thiram, diethyldithiocarbamate and carbon disulfide [Abstract], Pharmacologist 20 213. 

Masuda Y, Yasoshima M, Shibata K. 1988. Effects of carbon disulfide, diethyldithiocarbamate, and disulfiram on drug metabolism in the perfused rat liver. Res Commun Chem Pathol Pharmacol 61 65-82. 

Wells J, Koves E. 1974. Detection of carbon disulfide (a disulfiram metabolites) in expired air by gas chromatography. J Chromatogr 92 442-444. 

Disulfiram (tetraethylthiuram disulfide Antabuse) was taken in the course of an investigation of its potential anthelmintic efficacy by two Danish physicians, who became iU at a cocktail party and were quick to realize that the compound had altered their responses to alcohol. They initiated a series of pharmacological and clinical studies that provided the basis for the use of disulfiram as an adjunct in the treatment of chronic alcohohsm. Similar responses to alcohol ingestion are produced by various congeners of disulfiram, namely, cyanamide, the fungus Coprinus atramentarius, the hypoglycemic sulfonylureas, metronidazole, certain cephalosporins, and animal charcoal. 

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