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May 18, 1940


JAMA. 1940;114(20):2020-2021. doi:10.1001/jama.1940.02810200048011

Ever since urea was prepared synthetically by Wöhler in 1828 its derivatives have occupied an important place in medicine and in research. Urea, as an amino compound, may be readily combined with acids. A classic example of synthesizing is the so-called malonic acid synthesis, in which urea and malonic acid combine to form malonylurea (barbituric acid). This has been the basis of many of the hypnotic agents, particularly those belonging to the barbital series. By replacing the ethyl groups with other alkyl or aromatic groups it is possible theoretically to obtain more than 1,200 barbital derivatives.

In 1903 barbital (diethylbarbituric acid) was first introduced into medicine by Fischer and von Mering under the proprietary name of veronal. Its introduction was followed in 1913 by phenobarbital (luminal), which in turn was rapidly followed by other salts of the malonylureas. After the war of 1914-1918 a rush to produce modifications of the original compound that were not covered by German patents became widely apparent. Not until 1923, however, was the intravenous and intramuscular use of the soluble salts of barbital derivatives introduced. Since then the use of the malonylureas has been extensive among the medical profession and self administration by the public has brought about abuse. The effectiveness of barbital and