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  Oct 01, 2018

Barbiturate History

Sleep disorders have been managed using several means throughout the history of mankind. It all began with alcohol and alkaloids of opium and other narcotic plants (hemp, belladonna, henbane, etc). It was in the late 19th and early 20th centuries that drugs such as paraldehyde, chloral hydrate, and bromides were developed for induction and maintenance of sleep.

In 1864 Adolf von Bayer developed malonylurea from which in the early 20th century came the barbiturates. These agents were first brought to the market in 1904 by Farbwerke Fr Bayer and Co.

Barbiturates are basically a closed-chain ureic compound, whose nucleus is malonylurea. Malonyurea is a combination of urea and malonic acid, an acid derivative taken from apples.

Barbiturates were synthesized in 1864 by Adolf von Baeyer. The process was then perfected by the French chemist Edouard Grimaux in 1879.

Origin of the term barbiturates

There are several speculations about the origin of the term barbiturates. Some suggest it was a name given by Baeyer in honor of his friend Barbara.

Yet others suggest that Baeyer celebrated his discovery of these compounds in a tavern near his home that was frequented by artillery officers. These officers were celebrating the day of their patron, St Barbara. The name could have come from there.

Another possibility of the name was that the name came from the “barbed” appearance of the molecule due to the appearance of the crystals of these ureic compounds.

Revolution in psychiatric and neurological disorders

The first agent of this class was diethyl-barbituric acid. This spelled a revolution in psychiatric and neurological disorders of the time.

It was successfully used in many patients with serious neuroses and psychoses. They were one of the first agents to be used in controlling seizures and in inducing sleep in insomniacs.

With time barbiturates started the era of intravenous anesthetic agents. Before thiopentone, general anesthesia meant induction using the gases like nitrous oxide.

Barbiturates in the 20th century

Over the initial years of the 20th century more than 2,500 barbiturates were synthesized. Of these 50 were eventually employed clinically. Their use spread wide before physicians became aware of their risk of dependence and abuse liability.

It was in 1912 that the first cases of dependence on barbiturates were reported from Germany. After initial reports, more physicians reported delirium and withdrawal symptoms on abrupt discontinuation or dose reduction of barbiturates.

It was in 1950 that researchers published a paper that finally established that physical dependence on barbiturates is a possibility that can be induced in the laboratory as well in experimental conditions.

What was surprising was that despite use of barbiturates for over five decades, it was only in the 1950’s that barbiturates were accepted as drugs that could cause dependence.

It took another two decades for the physicians to be aware that these agents could cause dependence and abuse and should be prescribed only sparingly in select cases.

Today 5 or 6 derivates of barbiturates are still being used as inducers of general anesthesia and serious forms of insomnia and in some types of epilepsy.