Barbital (as known in the United States) or barbitone (as known elsewhere), marketed under the brand names Veronal for the pure acid and Medinal for the sodium salt, was the first commercially available barbiturate. It was used as a sleeping aid (hypnotic) from 1903 until the mid-1950s. The chemical names for barbitone are diethylmalonyl urea or diethylbarbituric acid; hence, the sodium salt (known as medinal, a genericised trademark in the United Kingdom), is known also as sodium diethylbarbiturate. Barbitone was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethoxide, and then by adding at least two molar equivalents of ethyl iodide to the silver salt of malonylurea or possibly to a basic solution of the acid. The result was an odorless, slightly bitter, white crystalline powder.
Barbitone was first synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering. They published their discovery in 1903 and it was marketed in 1904 by the Bayer company as “Veronal”. A soluble salt of barbitone was marketed by the Schering company as “Medinal.” It was dispensed for “insomnia induced by nervous excitability”.[unreliable source?] It was provided in either capsules or cachets. The therapeutic dose was ten to fifteen grains (0.65-0.97 grams). 3.5 to 4.4 grams is the deadly dose but sleep has also been prolonged up to ten days with recovery.
Barbitone was considered to be a great improvement over the existing hypnotics. Its taste was slightly bitter, but an improvement over the strong, unpleasant taste of the commonly used bromides. It had few side effects. Its therapeutic dose was far below the toxic dose. However, prolonged usage resulted in tolerance to the drug, requiring higher doses to reach the desired effect. Fatal overdoses of this slow acting hypnotic were not uncommon. Pioneering aviator Arthur Whitten Brown (of "Alcock and Brown" fame) died of an accidental overdose.
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Fischer, Emil and Joseph von Mering, “Ueber eine neue Klasse von Schlafmitteln”, Therap Gegenw 44:97-101, 1903.
"Veronal", in Finley, Ellingwood, M.D. The American Materia Medica, Therapeutics and Pharmacognosy", 1919. , accessed 07 Nov 2005.
(English) Dombrowski SM, Krishnan R, Witte M,Maitra S, Diesing C, et al. 1998. Constitutive and barbital-induced expression of the CYP6A2 allele of a high producerstrain of CYP6A2 in the genetic backgroundof a low producer strain. Gene221:69–77.