Barbital (or barbitone), sold 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 barbital are diethylmalonyl urea or diethylbarbituric acid; hence, the sodium salt is known also as sodium diethylbarbiturate.
Synthesis
Barbital, then called "Veronal", was first synthesized in 1902 by German chemists Emil Fischer and Joseph von Mering, who published their discovery in 1903.
Barbital was prepared by condensing
Diethyl malonate with
urea in the presence of
sodium ethoxide, or by adding at least two molar equivalents of
ethyl iodide to the silver salt of
Barbituric acid or possibly to a basic solution of the acid. The result was an odorless, slightly bitter, white crystalline powder.
Its introduction followed the investigations of Fischer and von Mering on the pharmacological properties of certain open and closed (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), and propylbarbital. All three were found to be hypnotics: the first was about equal in power to the already-known sulphonal (now sulfonmethane), whilst the third was four times as powerful, but its use was attended by prolonged after-effects. Veronal was found to be midway.
Barbital can also be synthesized in a condensation reaction from urea and diethyl-2,2-diethylmalonate, a diethyl malonate derivative:
Marketing
Barbital was marketed in 1904 by
Bayer as "Veronal," while the soluble salt of barbital was marketed by
Schering AG as "Medinal." It was dispensed for "
insomnia induced by nervous excitability."
It was provided in either crystal form or in capsules. The therapeutic dose was ten to fifteen grains (0.6–1
). 3.5 to 4.4 grams (55 to 68 grains) is considered the lethal dose.
Pharmacology
Barbital was considered to be a great improvement over the existing
Hypnotic. Its taste was slightly bitter, but better than the strong, unpleasant taste of the commonly used
. 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 tsarina Alexandra Feodorovna confessed to a friend.
Fatal overdoses of this slow-acting hypnotic were common. Pioneering aviator Arthur 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 via GABAA receptor and reversible photoisomerization in water using cyclodextrin.
pH buffer
Solutions of sodium barbital have also been used as
Buffer solution for biological research, e.g., in immunoelectrophoresis or in fixative solutions.
As barbital is a controlled substance, barbital-based buffers have largely been replaced by other substances.
Poisoning
Japanese writer Ryūnosuke Akutagawa deliberately overdosed on the drug in 1927, as did
Un Chien Andalou actor
Pierre Batcheff in 1932,
Hungary poet Gyula Juhász in 1937,
Germany mathematician Felix Hausdorff in 1942, Austrian writer
Stefan Zweig in 1942,
France Anarchism Germaine Berton in 1942,
and Greek musician
Attik in 1944. During
the 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
[I Will Bear Witness by Victor Klemperer (Author), Martin Chalmers (Translator) 1998] Regime.
, 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.
Eric Mareo, son of playwright Raimund Pechotsch, murdered his wife Thelma with Veronal. Thelma's lesbian lover Freda Stark was a key witness at the trial.
In fiction
In the D. H. Lawrence story,
The Lovely Lady, the titular character dies from a self-administered overdose.
Barbital, under the name of Veronal, has been used as a plot device in the author Agatha 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).
It was used as a method of suicide in Stephen King The Stand by a character named Perion after her partner Mark dies from appendicitis.
Further reading
