 | Barbituric acid (malonylurea) |
Barbiturates are derivatives of barbituric acid. They can be used as hypnotics, sedatives, anticonvulsants and anesthetics, although they are probably most familiar as 'sleeping pills'. The different properties of the various barbiturates depend upon the sidegroups attached to the ring.
| | Barbituric acid (malonylurea) |
Barbituric acid was first discovered by the German chemist Adolf von Baeyer in 1864 by combining urea (an animal waste product) with malonic acid (derived from the acid of apples). There are several stories about how it got its name, the most likely of which is that von Baeyer and his colleagues went to celebrate their discovery in a tavern where the town's artillery garrison were also celebrating the day of Saint Barbara - the patron saint of artillerists. An artillery officer is said to have christened the new substance by amalgamating 'Barbara' with 'urea'.
 | Barbituric acid is made by combining malonic acid (left) with urea (right), with the elimination of two water molecules (shown in red). |
Barbituric acid, itself, is not pharmacologically active, but chemists immediately began making a great variety of derivatives for potential use as drugs. The medical value of these substances was not realised, however, until 1903 when two other German chemists, Emil Fischer and Joseph von Mering, discovered that one of these compounds, diethylbarbituric acid, was very effective in putting dogs to sleep. It is said that von Mering proposed that the new substance be called 'Veronal', because the most peaceful place he knew on Earth was the Italian city of Verona.
When this discovery was announced, chemists rapidly produced many new medically active barbiturates, including the sleeping pill phenobarbital (sold under the tradename Luminal), and pentobarbitone (Nembutal) which is often used to induce sleepiness before full pre-operative anesthesia. By 1955 the production of barbiturates in the US alone amounted to enough to provide 10 million adults with a sleeping pill every night of the year!
 |  |  |
| Barbital (Veronal) | Phenobarbital (Luminal) | Pentobarbital (Nembutal) |
| Various barbiturates. The differences from barbituric acid are shown in red. |
We still do not know how barbiturates work, although it is believed that they act by depressing the central nervous system and inhibiting certain nerve response centres. We do know, however, that their physiological effects are very structure dependent. The basic structure is a ring composed of 4 carbon atoms and 2 nitrogens. Certain sidechains added to the ring can dramatically alter the potency of the drug - indeed, in some cases the addition of a single carbon atom transforms an inactive form of the compound into an active one.
One class of barbiturate derivatives is called thiobarbiturates, which contain a sulphur molecule in place of one of the oxygens. The most important member of this class is sodium pentothal, which is used as an intravenous anesthetic from which recovery is rapid and which has the advantage of having very little or no side effects.
 | Sodium pentothal - the 'truth serum'. The changes from barbituric acid are shown in red. |
Barbiturates, particularly sodium pentothal, also have interesting applications in the field of psychology, since they can provide access to levels of consciousness not normally attainable except in dreams or trances. This allowed them to be used for therapy of traumatised GIs in WW2 who could relive and verbalise battle experiences which were buried beyond voluntary recollection. The inhibition-relieving action of these drugs has also been employed by the police (and other agencies), allowing prisoners that have been placed into a pentothal-induced dreamy trance to volunteer information they otherwise would have suppressed. This has earned sodium pentothal the nickname of a 'truth serum', even though in actuality it is neither a serum, nor does it guarantee the truth.
Barbiturates present problems because patients develop tolerance for them and even higher doses are then required to produce the same effect. They are also habit forming, and the fatal dose is not much more than the normal therapeutic dose. Thus they are truly dangerous drugs and are widely used by suicides. They also present the danger of automatism, that is the patient may take a dose, leave the bottle on the bedside table, and then, when half asleep, forget that the dose has already been taken and take some more. This is one of the theories for the death of Marilyn Monroe. Another major problem is that barbiturates and alcohol are eliminated by the same system of enzymes in the liver. This means that consumption of the 2 chemicals at the same time can lead to a build up of the toxic drug in the liver, resulting in liver failure and death.