Avinash De Sousa - Disulfiram: Its Use in Alcohol Dependence and Other Disorders

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This is a unique and one of its kind book dedicated to a drug named Disulfiram, which has been used in the management of alcohol dependence for the past six decades. The book has eight chapters and traces the history of evolution of Disulfiram, its mechanism of action, its role in alcohol and cocaine dependence, its side effects and toxicity, its use in special populations and its future with certain ethical issues. The book will serve to help clinicians and students alike in understanding various facets of Disulfiram and its usage.

This book is dedicated to my late father Prof. Dr. Alan De Sousa who introduced me to Disulfiram and with whom my early work in Disulfiram is associated.

I am sure readers will enjoy reading the book as much I have enjoyed writing it.

The early history shall trace how the effect of disulfiram on ethanol metabolism and its action was discovered, how it came to be marketed as an agent for the treatment of alcohol dependence and the early clinical use of the molecule. It is worthwhile mentioning that the discovery of Disulfiram was by serendipity, which then changed the face of alcohol dependence management for many years to come. While the discovery of disulfiram as a drug has been dated as the late 1940s, the drug has been known in medicine since the late 1800s. A German chemist Grodzki, reported in 1881, about a new compound synthesized from thiocarbamide [].

Disulfiram was also used in the 1940s by dermatologists for the treatment of scabies. In 1942 two British physicians concluded that it was indeed a useful drug for the management of scabies. The effect of the disulfide in destroying scabies and intestinal worms was investigated in Sweden in 1943 when disulfiram was used in the management of animals infested with worms and scabies. Pharmacological companies at that time began marketing the drug for animal and human scabies manifestations [].

In 1934, Erik Jacobsen was the head of a pharmaceutical company and its biomedical research unit in Copenhagen. He was appointed in 1962 as professor of pharmacology at the Pharmaceutical College, an institution established in 1892 and merged with the University of Copenhagen. Jacobsens research area was problems of cell oxidation, and he discovered that the anti-scabies effect of disulfiram was due to its ability to absorb copper and form chelates with the metal. Animal experiments revealed that the drug would work also for intestinal worms. The experiments confirmed that the drug was a vermicide. Human experimentation for disulfiram as a vermicide was yet to be done []. Thus in a few days it was confirmed that disulfiram has adverse effects on human beings when they ingested alcohol.

In 1945, Jacobsen and his collaborators realized that disulfiram had the potential to be used as a drug for long-term treatment of alcohol dependence but they did not follow up the idea. Alcohol dependence at that time was not a public health issue in Denmark, and an alcohol-deterrent drug was of little commercial interest to the pharmaceutical industry []. Enzyme studies had proved that oxidation of acetaldehyde, the first step in the metabolism of ethanol, was impeded by disulfiram in human subjects.