Dinitrophenol and bioenergetics: An historical perspective

Summary

The subject of the paper is the history of dinitrophenol compounds in relationship to bioenergetics. The history of the interaction between dinitrophenols and bioenergetics can be traced back to 1885 whenCazeneuve andLÉpine discovered the thermogenic effects of dinitronapthol. Dinitronapthol and dinitrocresol were used as food colors in the late 19th century although a growing awareness of their toxic properties led to the prohibition of their use for this purpose in certain countries. The toxicity of dinitrophenol was studied in some detail byMayer and his colleagues in France during World War I since it was used by the French in the manufacture of munitions. They recognized that the compound stimulated cellular metabolism, but they did not publish their results until many years later and as a result their work was at first not widely known. In the late 1920's and early 1930's, CorneilleHeymans and his colleagues at Ghent andCutting andTainter and their colleagues at Stanford demonstrated the metabolic stimulating powers of dinitronapthol and dinitrophenol. The Stanford group introduced dinitrophenol into therapeutics for the treatment of obesity, and the drug soon found its way into numerous “anti-fat” patent medicines. Several fatalities, a number of cases of cataract, and other reported toxic effects led to widespread concern about the use of dinitrophenol. The FDA could not take effective action against the drug, however, until after its powers had been expanded by the 1938 Food, Drug and Cosmetic Act. The use of dinitrophenol and related compounds for treating obesity was essentially discontinued after the 1930's. Studies on the mode of action of dinitrophenol in the 1930's and 1940's led ultimately to the establishment of the fact that it uncouples oxidative phosphorylation (Loomis andLipmann, 1948).