Disulfiram and Its Metabolite, Diethydithiocarbamate

The widely-used drug disulfiram metabolizes rapidly to form diethyldithiocarbamate, and it is impossible to study its metabolic rate inhibitory action on acetaldehyde metabolism without considering the properties of the metabolite, even though they have different spectra of pharmacological activity and different applications. Diethyldithiocarbamate is pharmacologically active in a greater number of ways than had been originally suggested. Its uses have ranged from an antidote to nickel carbonyl intoxication to the balancing of mossy fibre botons in the hypothalamus, and from its application as a rescue agent in cancer chemotherapy to its recently confirmed ability to inhibit the progression of HIV infections. There is sustained interest in its ability to chelate heavy metals, particularly cadmium, thallium and nickel, and whilst it continues to be used experimentally in cisplatin chemotherapy for protection against renal toxicity, there is now increasing interest in its ability to counteract bone marrow toxicity of a range of chemotherapeutic agents. There has been a recent increase in the use of disulfiram in the treatment of alcoholism, it having been credited with affecting a marked decrease in the incidence of cases requiring treatment for this condition. The growing level of research and clinical interest in disulfiram and diethyldithiocarbamate has resulted in a need for an integrated synthesis of current knowledge on the subject. This book provides a critical review of the current status of research in the properties, pharmacology and toxicology of disulfiram and diethyldithiocarbamate and their use for the treatment of a variety of human disease conditions, including AIDS, cancer, alcoholism and heavy metal intoxication. The text is supported by a bibliography and the book should serve as an important reference source for pharmacologists, biomedical scientists, immunologists, biochemists and clinicians.