Barbiturates are drugs that act as central nervous system depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. Some are also used as anticonvulsants.

Barbiturates are derivatives of barbituric acid.

History

Barbituric acid was first synthesised on December 4, 1864, by German researcher Adolf von Baeyer. This was done by condensing urea (an animal waste product) with diethyl malonate (an ester derived from the acid of apples). There are several stories about how the substance got its name. The most likely story 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.^[1]

Barbituric acid itself is not pharmacologically active, but chemists immediately began making a great variety of derivatives for potential use as drugs. No substance of medical value was discovered, however, until 1903 when two German chemists working at Bayer, Emil Fischer and Joseph von Mering, discovered that barbital was very effective in putting dogs to sleep. Barbital was then marketed by Bayer under the trade name Veronal. It is said that Von Mering proposed this name because the most peaceful place he knew was the Italian city of Verona.^[1]

In 1912, Bayer introduced another barbituric acid derivative, phenobarbital, under the trade name Luminal, as a sedative-hypnotic.

In the 1950s and 1960s, reports began to be published about side effects and dependence related to barbiturates.

In 1970 several barbiturates were designated in the United States as controlled substances with the passage of the American Controlled Substances Act of 1970. Pentobarbital, secobarbital and amobarbital were designated schedule II drugs, butabarbital schedule III, and barbital and phenobarbital schedule IV.

In 1971 the Convention on Psychotropic Substances was signed in Vienna. Designed to regulate amphetamines, barbiturates, and other synthetics, the treaty today regulates amobarbital (schedule III), butalbital (III), cyclobarbital (III), pentobarbital (III), allobarbital (IV), methylphenobarbital (IV), phenobarbital (IV), secobarbital (IV), and vinylbital (IV) as scheduled substances.

Mechanism of action

The principal mechanism of action of barbiturates is believed to be their affinity for the GABA_A receptor (Acts on GABA : BDZ receptor cl^- channel complex). GABA is the principal inhibitory neurotransmitter in the mammalian Central Nervous System (CNS). Barbiturates bind to the GABA_A receptor at the alpha? or the beta? sub unit, which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABA-ergic effect, barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABA_A receptors and inhibit excitatory AMPA receptors can explain the CNS-depressant effects of these agents. At higher concentration they inhibit the Ca²⁺ dependent release of neurotransmitters. ^[2]

Therapeutic use

Barbiturates like pentobarbital and phenobarbital were long used as anxiolytics and hypnotics. Today benzodiazepines have largely supplanted them for these purposes, because benzodiazepines have less potential for abuse and less danger of lethal overdose. Today, fewer than 10 percent of all sedative/hypnotic prescriptions in the United States are for barbiturates.Barbiturates are still widely used in surgical anesthesia, especially to induce anesthesia.Phenobarbital is used as an anticonvulsant for people suffering from seizure disorders such as febrile seizures, tonic-clonic seizures, status epilepticus, and eclampsia.^[3]

Effects on the body

Barbiturates are classified as ultrashort-, short-, intermediate-, and long-acting, depending on how quickly they act and how long their effects last.^[4] Ultrashort barbiturates such as thiopental (Pentothal) produce unconsciousness within about a minute of intravenous (IV) injection. These drugs are used to prepare patients for surgery; other general anesthetics like nitrous oxide are then used to keep the patient from waking up before the surgery is complete. Because Pentothal and other ultrashort-acting barbiturates are typically used in hospital settings, they are not very likely to be abused, noted the DEA.^{[5]Secobarbital (marketed by Eli Lilly and Company under the brand name Seconal®) is a barbiturate derivative drug. It possesses anaesthetic, anticonvulsant, sedative and hypnotic properties. In the United Kingdom, it was known as Quinalbarbitone.}

Abusers tend to prefer short-acting and intermediate-acting barbiturates.^[6] The most commonly abused are amobarbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal). A combination of amobarbital and secobarbital (called Tuinal) is also highly abused. Short-acting and intermediate-acting barbiturates are usually prescribed as sedatives and sleeping pills. These pills begin acting fifteen to forty minutes after they are swallowed, and their effects last from five to six hours. Veterinarians use pentobarbital to anesthetise animals before surgery; in large doses, it can be used to euthanise animals.^[5]

Long-acting barbiturates such as phenobarbital (Luminal) and mephobarbital (Mebaral) are prescribed for two main reasons. When taken at bedtime, they help treat insomnia. When taken during the day, they have sedative effects that can aid in the treatment of tension and anxiety. These same effects have been found helpful in the treatment of convulsive conditions like epilepsy. Phenobarbital has also been used in the treatment of delirium tremens during alcohol detoxification, although benzodiazepines have a more favorable safety profile and are more often used.^[7] Long-acting barbiturates take effect within one to two hours and last 12 hours or longer.^[5]

External links

• U.S. Drug Enforcement Administration Source for some public domain text used on this page.
• Erowid.org - Barbiturates
• Chemcases profile
• Barbiturate history and chemistry

References