THE DISCOVERY OF ANTABUSE

HALD, JENS, et al.

The Sensitizing Effect of Tetraethylthiuramdisulphide (Antabuse) to Ethylalcohol.

Köbenhavn [Copenhagen], Einar Munksgaard, 1948. Royal8vo. Bound with the original front wrapper in a nice contempoaray half cloth with gil lettering to spine. In "Acta Pharmacologica et Toxicologica", Vol. 4. Entire volume offered. A very fine and clean copy, near mint. Pp. 285-96. [Entire volume: (2), X, 400, (2), 189 pp.].

First printing of Hald's seminal paper in which he first introduced antabuse in the treatment of alcoholism. Antabuse (also known as disulfiram) was the first drug to be approved by the U.S. Food and Drug Administration for treatment of alcohol dependence. Today it is the most widely used drug to prevent alcoholism and it is estimated that some 120,000 persons throughout the world take antabuse each year.

"In 1945 Danish researchers observed that the substance caused very unpleasant physiological effects in persons who had consumed alcohol. A few years later this chance observation was turned into a profitable production of pills used to combat alcoholism (antabuse = anti-abuse)." (Kragh, From Disulfiram to Antabuse: the Invention of a Drug).

The discovery of Antabuse was essentially an accident since it was intended to provide a remedy for parasitic infestations: "Copenhagen's Dr. Erik Jacobsen, 45, likes to try out new drugs on himself before giving them to his patients. One night before going to a dinner party he swallowed a couple of pills made of tetraethylthiuram- disulfide; they were supposed to be good for intestinal worms. To his surprise, Dr. Jacobsen found that any form of alcohol revolted him. When he sipped even a small glass of beer, his face got red, his heart started to pound, and he had trouble getting his breath." (Time, December 6, 1948)

"Antabuse [trade name for disulfiram], a chemical which prevents the body from fully processing alcohol. It does this by blocking the action of aldehyde dehydrogenase, a key enzyme in the metabolic pathway of ethanol, and thereby causing a build-up of the toxic by-product acetaldehyde, with extremely unpleasant consequences for patients. People with active disulfiram in their bodies experience flushing, nausea and high blood pressure soon after drinking." (Raikhel, Images from the history of disulfiram treatment)

"The most important journal for the dissemination of knowledge concerning the actions of antabuse in the organism was the Acta Pharmacologica et Toxicologica, an international journal founded in 1945 and edited by Scandinavian scientists. The fact that it was published in Copenhagen and that Jacobsen was among the editors made it an ideal journal for publishing new research related to antabuse. For example, Vol. 4 of 1948 included two substantial papers by Hald and Jacobsen on the formation and action of acetaldehyde; and their collaborator Erik Rasmussen, a pharmacologist associated with Medicinalco, reported his investigations of the action of the antabuse-alcohol reaction on the blood circulation and respiration. (Kragh, From Disulfiram to Antabuse: the Invention of a Drug).

Garrison & Morton no. 2091.

Order-nr.: 50119