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| Trade names | Veronal, Medinal |
| AHFS/Drugs.com | International Drug Names |
| MedlinePlus | a682221 |
| Routes of administration | By mouth |
| Drug class | Barbiturate |
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| Eliminationhalf-life | 30.3 (± 3.2) hours |
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| ECHA InfoCard | 100.000.301 |
| Chemical and physical data | |
| Formula | C8H12N2O3 |
| Molar mass | 184.195 g·mol−1 |
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Barbital (orbarbitone), sold under the brand namesVeronal for the pure acid andMedinal for the sodium salt, was the first commercially availablebarbiturate. It was used as a sleeping aid (hypnotic) from 1903 until the mid-1950s. The chemical names for barbital are diethylmalonyl urea or diethylbarbituric acid; hence, the sodium salt is known also as sodium diethylbarbiturate.
Barbital, then called "Veronal", was first synthesized in 1902 by German chemistsEmil Fischer andJoseph von Mering, who published their discovery in 1903.[2] Barbital was prepared by condensingdiethylmalonic ester withurea in the presence ofsodium ethoxide, or by adding at least two molar equivalents ofethyl iodide to the silver salt ofmalonylurea (barbituric acid) or possibly to a basic solution of the acid. The result was an odorless, slightly bitter, white crystalline powder.[3]
Its introduction followed the investigations of Fischer and von Mering on the pharmacological properties of certain open and closedacylureas (then called ureides). Led by the impression that hypnotic action appears to be largely dependent on the presence of ethyl groups, they prepared diethylacetyl urea, diethylmalonyl urea (i.e., Barbital itself), anddipropylmalonyl urea. All three were found to be hypnotics: the first was about equal in power to the already-known sulphonal (nowsulfonmethane), whilst the third was four times as powerful, but its use was attended by prolonged after-effects. Veronal was found to be midway.[3]
Barbital can also be synthesized in acondensation reaction fromurea anddiethyl-2,2-diethylmalonate, adiethyl malonate derivative:
Barbital was marketed in 1904 byBayer as "Veronal," while the soluble salt of barbital was marketed bySchering as "Medinal." It was dispensed for "insomnia induced by nervous excitability."[4][unreliable source?] It was provided in either crystal form or incapsules. The therapeutic dose was ten to fifteengrains (0.6–1grams).[citation needed] 3.5 to 4.4 grams (55 to 68 grains) is considered the lethal dose.[citation needed]
Barbital was considered to be a great improvement over the existinghypnotics. Its taste was slightly bitter, but better than the strong, unpleasant taste of the commonly usedbromides. It had few side effects, and 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. "I'm literally saturated with it", the Russian tsarinaAlexandra Feodorovna confessed to a friend.[5] Fatal overdoses of this slow-acting hypnotic were common. Pioneering aviatorArthur Whitten Brown (of "transatlantic flight of Alcock and Brown" fame) died of an accidental overdose.
A photoswitchable derivative of barbital based on a donor-acceptor Stenhouse adduct (DASA) has been developed for research purposes (photopharmacology). DASA-barbital shows neuronal activity viaGABAA receptors and reversiblephotoisomerization in water usingcyclodextrin.[6]
Solutions of sodium barbital have also been used aspH buffers for biological research, e.g., inimmunoelectrophoresis or in fixative solutions.[7][8] As barbital is a controlled substance, barbital-based buffers have largely been replaced by other substances.[9]
Japanese writerRyūnosuke Akutagawa deliberately overdosed on the drug in 1927, as didUn Chien Andalou actorPierre Batcheff in 1932,Hungarian poetGyula Juhász in 1937,GermanmathematicianFelix Hausdorff in 1942,Austrian writerStefan Zweig in 1942,FrenchAnarchistGermaine Berton in 1942,[10] and Greek musicianAttik in 1944. Duringthe Holocaust, many Jewish residents of Berlin, Dresden, Wiesbaden, and other German cities used Veronal to take their lives by suicide to avoid deportation to concentration camps by the Nazi[11] Regime.[12]Alfred Kerr, a German theatre critic and essayist, suffered a stroke on a trip to Germany after WWII and decided to end his own life via an overdose of Veronal, which was procured for him by his wife.[13]
Eric Mareo, son of playwright Raimund Pechotsch, murdered his wife Thelma with Veronal. Thelma's lesbian loverFreda Stark was a key witness at the trial.[14]
In theD. H. Lawrence story,The Lovely Lady, the titular character dies from a self-administered overdose.[15]
Barbital, under the name of Veronal, has been used as a plot device in the authorAgatha Christie's murder mysteries.
Barbital was also used as a plot device in the CBS television legal drama,Perry Mason, in the episode,The Case of the Missing Element (1963).[16]
It was used as a method ofsuicide inStephen King’sThe Stand by a character named Perion after her partner Mark dies from appendicitis.[citation needed]
One or more of the preceding sentences incorporates text from a publication now in thepublic domain: Chisholm, Hugh, ed. (1911). "Veronal".Encyclopædia Britannica. Vol. 27 (11th ed.). Cambridge University Press. p. 1037.
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