Barbital (or barbitone), marketed under the brand names Veronal for the pure acid and Medinal for the sodium salt, was the first commercially available

barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential a ...

. It was used as a sleeping aid (

hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...

) from 1903 until the mid-1950s. The chemical names for barbital 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.

Synthesis

Barbital, then called "Veronal", was first synthesized in 1902 by German chemists

Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fischer projection, a symbolic way of draw ...

and

Joseph von Mering Josef, Baron von Mering (28 February 1849, in Cologne – 5 January 1908, at Halle an der Saale, Germany) was a German physician. Working at the University of Strasbourg, Mering was the first person to discover (in conjunction with Oskar Minkow ...

, who published their discovery in 1903. Barbital was prepared by condensing diethylmalonic ester with

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...

in the presence of sodium ethoxide, or by adding at least two molar equivalents of ethyl iodide to the silver salt of malonylurea (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 acylureas (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 dipropylmalonyl urea. 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 In organic chemistry, a condensation reaction is a type of chemical reaction in which two molecules are combined to form a single molecule, usually with the loss of a small molecule such as water. If water is lost, the reaction is also known as a ...

from

and diethyl-2,2-diethylmalonate, a diethyl malonate derivative: :

Marketing

Barbital was marketed in 1904 by the

Bayer Bayer AG (, commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and one of the largest pharmaceutical companies in the world. Headquartered in Leverkusen, Bayer's areas of business include pharmaceutic ...

company as “Veronal”. A soluble salt of barbital was marketed by the Schering company as “Medinal.” It was dispensed for “

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

induced by nervous excitability”. It was provided in either crystal form or in cachets (capsules). The therapeutic dose was ten to fifteen grains (0.6-1

gram The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...

s). 3.5 to 4.4 grams (55 to 68 grains) is the deadly dose but sleep has also been prolonged up to ten days with recovery.

Pharmacology

Barbital was considered to be a great improvement over the existing hypnotics. Its taste was slightly bitter, but better than the strong, unpleasant taste of the commonly used

bromide A bromide ion is the negatively charged form (Br−) of the element bromine, a member of the halogens group on the periodic table. Most bromides are colorless. Bromides have many practical roles, being found in anticonvulsants, flame-retardant ...

s. 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 not uncommon. 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 GABA_A receptors and reversible

photoisomerization In chemistry, photoisomerization is a form of isomerization induced by photoexcitation. Both reversible and irreversible photoisomerizations are known for photoswitchable compounds. The term "photoisomerization" usually, however, refers to a re ...

in water using cyclodextrin.

pH buffer

Solutions of sodium barbital have also been used as pH buffers for biological research, e.g., in

immunoelectrophoresis Immunoelectrophoresis is a general name for a number of biochemical methods for separation and characterization of proteins based on electrophoresis and reaction with antibodies. All variants of immunoelectrophoresis require immunoglobulins, ...

or in fixative solutions. As barbital is a controlled substance, barbital-based buffers have largely been replaced by other substances.

Suicide

Japanese writer Ryūnosuke Akutagawa deliberately overdosed on the drug in 1927, as did ''

Un Chien Andalou ''Un Chien Andalou'' (, ''An Andalusian Dog'') is a 1929 French silent short film directed by Luis Buñuel, and written by Buñuel and Salvador Dalí. Buñuel's first film, it was initially released in a limited capacity at Studio des Ursuline ...

'' actor

Pierre Batcheff Pierre Batcheff (Russian: Пьер Батчефф; 23 June 1901? – 13 April 1932) was a French actor of Russian origin. He became a popular film actor from the mid-1920s until the early 1930s, and among his best-known work was the surrealist sh ...

in 1932, Austrian writer

Stefan Zweig Stefan Zweig (; ; 28 November 1881 – 22 February 1942) was an Austrian novelist, playwright, journalist, and biographer. At the height of his literary career, in the 1920s and 1930s, he was one of the most widely translated and popular write ...

in 1942,

French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...

Anarchist Anarchism is a political philosophy and movement that is skeptical of all justifications for authority and seeks to abolish the institutions it claims maintain unnecessary coercion and hierarchy, typically including, though not necessar ...

Germaine Berton Germaine Berton (7 June 1902, in Puteaux – 6 July 1942, in Paris) was a French anarchist and trade unionist. She is known for the murder of Marius Plateau, an editor for the ''Action Francaise'' journal and a leader in the royalist organisati ...

in 1942, and Greek musician Attik in 1944. During

The Holocaust The Holocaust, also known as the Shoah, was the genocide of European Jews during World War II. Between 1941 and 1945, Nazi Germany and its collaborators systematically murdered some six million Jews across German-occupied Europ ...

, many

Jewish Jews ( he, יְהוּדִים, , ) or Jewish people are an ethnoreligious group and nation originating from the Israelites Israelite origins and kingdom: "The first act in the long drama of Jewish history is the age of the Israelites""The ...

residents of Berlin, Dresden, Wiesbaden and other German cities used Veronal to commit suicide to avoid deportation to concentration camps by the Nazi Regime. 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 In the

D. H. Lawrence David Herbert Lawrence (11 September 1885 – 2 March 1930) was an English writer, novelist, poet and essayist. His works reflect on modernity, industrialization, sexuality, emotional health, vitality, spontaneity and instinct. His best-k ...

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 Dame Agatha Mary Clarissa Christie, Lady Mallowan, (; 15 September 1890 – 12 January 1976) was an English writer known for her 66 detective novels and 14 short story collections, particularly those revolving around fiction ...

's murder mysteries. In Stephen King's "The Stand", some characters used Veronal in small doses as a way to suppress the ever-intensifying nightmares involving the "dark man" they communally experienced. The main character in

Dorothy Parker Dorothy Parker (née Rothschild; August 22, 1893 – June 7, 1967) was an American poet, writer, critic, and satirist based in New York; she was known for her wit, wisecracks, and eye for 20th-century urban foibles. From a conflicted and unhap ...

's short story ''Big Blonde'', Hazel Morse, buys 2 bottles of Veronal tablets over the counter with the intention of committing suicide. In Miroslav Krleža's drama "Messrs. Glembay", Irena Danielli-Basilides overdosed on Veronal as her third and fatal suicide attempt.

Synthesis

Marketing

Pharmacology

pH buffer

Suicide

References

Further reading