Adolf von Baeyer (1835–1917), Josef von Mering (1849–1908), Emil Fischer (1852–1919)
MOTHER OF ALL BARBITURATES. Adolf von Baeyer went to a Munich tavern on December 4, 1864, St. Barbara’s Day, to celebrate. He had successfully synthesized malonylurea, which—likely in honor of St. Barbara—he termed barbituric acid. He could not have realized at the time how significant his finding would be to the practice of medicine.
Barbital, the first barbituric acid derivative, was introduced into therapy as a sleep-producing and antiseizure barbiturate in 1903 by the German chemist Emil Fischer and physician Josef von Mering. An etymological controversy surrounds the derivation of barbital’s trade name Veronal. Perhaps it was based on the Latin word verus (truth), an allusion to barbital being the true hypnotic. Then again, it might have referred to the Italian city of Verona, a peaceful vacation spot for von Mering.
Before barbital, there were the bromides (1857), chloral hydrate (1869), and paraldehyde (1882). After its appearance, barbital enjoyed widespread use for a decade until the appearance of phenobarbital (Luminal) in 1912, a drug that continues to be prescribed today. More than 2,500 derivatives of barbituric acid have been synthesized over the years, and about fifty of these were used for anxiety, insomnia, anesthesia, and seizure disorders. Barbiturates differ primarily with respect to their time of onset and their duration of action. Interestingly, the British refer to barbital as barbitone, preferring the suffix -one to the standard American and international barbiturate suffix of -al.
Barbiturates continued to be very widely used until the 1950s, when Librium, Valium, and related benzodiazepines appeared. The benzodiazepines were more specific, had fewer side effects and reduced potential to be abused, and were safer when taken in excessive doses, accidentally or intentionally.
Both Fischer and Baeyer were awarded Nobel Prizes in Chemistry, but not for their work on barbituric acid or barbiturates. Fischer significantly advanced our understanding of proteins and received the Prize in 1902 for his work on the chemistry and synthesis of sugars and purines. Among his many other accomplishments, Baeyer received the 1905 Prize for his synthesis of the indigo dye used in blue jeans.
SEE ALSO Bromides (1857), Chloral Hydrate (1869), Paraldehyde (1882), Phenobarbital (1912), Nembutal and Seconal (1928), Thiopental (1934), Librium (1960), Valium (1963).
Barbital and related barbiturates were initially promoted for producing restful and natural sleep. Research demonstrated that these drugs disrupted normal sleep patterns, however, leading to insomnia and disturbed sleep when abruptly stopped after long-term usage.