Barbiturate
Encyclopedia
Barbiturates are drugs that act as central nervous system depressant
s, and can therefore produce a wide spectrum of effects, from mild sedation
to total anesthesia
. They are also effective as anxiolytic
s, as hypnotic
s, and as anticonvulsant
s. Barbiturates also have analgesic
effects, however these effects are somewhat weak, preventing barbiturates from being used in surgery
in the absence of other analgesics. They have addiction potential, both physical and psychological. Barbiturates have now largely been replaced by benzodiazepine
s in routine medical practice - for example, in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous in overdose
. However, barbiturates are still used in general anesthesia, for epilepsy, and assisted suicide. Barbiturates are derivatives of barbituric acid
.
was first synthesized December 6, 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 apple
s). 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 feast of Saint Barbara
—the patron saint of artillerists. An artillery officer is said to have christened the new substance by amalgamating Barbara with urea. Another story holds that Von Baeyer synthesized the substance from the collected urine of a Munich waitress named Barbara. No substance of medical value was discovered, however, until 1903 when two German scientists 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
.
It was not until the 1950s that the behavioural disturbances and physical dependence potential of barbiturates became recognized.
While barbituric acid itself does not have any direct effect on the central nervous system
, chemists have derived over 2,500 compounds from it that possess pharmacologically active qualities. The broad class of barbiturates is further broken down and classified according to speed of onset and duration of action. Ultrashort-acting barbiturates are commonly used for anesthesia
because their extremely short duration of action allows for greater control. These properties allow doctors to rapidly put a patient "under" in emergency surgery situations. Doctors can also bring a patient out of anesthesia just as quickly, should complications arise during surgery. The middle two classes of barbiturates are often combined under the title "short/intermediate-acting." These barbiturates are also employed for anesthetic purposes, and are also sometimes prescribed for anxiety
or insomnia
. This is not a common practice anymore, however, owing to the dangers of long-term use of barbiturates; they have been replaced by the benzodiazepines for these purposes. The final class of barbiturates are known as long-acting barbiturates (the most notable one being phenobarbital, which has a half-life of roughly 92 hours). This class of barbiturates is used almost exclusively as anticonvulsants, although on rare occasions they are prescribed for daytime sedation. Barbiturates in this class are not used for insomnia, because, owing to their extremely long half-life, patients would awake with a residual "hang-over" effect and feel groggy.
Barbiturates can in most cases be used either as the free acid or as salts of sodium, calcium, potassium, magnesium, lithium, etc. Codeine
- and Dionine
-based salts of barbituric acid have been developed. In 1912, Bayer introduced another barbituric acid derivative, phenobarbital
, under the trade name Luminal
, as a sedative-hypnotic.
and phenobarbital
were long used as anxiolytics and hypnotics. Today, benzodiazepines have largely supplanted them for these purposes, because benzodiazepines have less potential for lethal overdoses
.
for euthanasia
and for capital punishment
by lethal injection
.
Thiopental is an ultra-short acting barbiturate that is marketed under the name Sodium Pentothal. It is often mistaken for "Truth Serum" or Sodium Amytal, an intermediate-acting barbiturate that is used for sedation and to treat insomnia, but was also used in so-called Sodium Amytal "interviews" where the person being questioned would be much more likely to provide the truth whilst under the influence of this drug. When dissolved in water, Sodium Amytal can be swallowed, or it can be administered by intravenous injection. The drug does not itself force people to tell the truth, but is thought to decrease inhibitions, making subjects more likely to be caught off guard when questioned.
is the principal inhibitory neurotransmitter in the mammal
ian central nervous system
(CNS). Barbiturates bind to the GABAA receptor at the alpha subunit, 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 GABAA 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.
Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.
Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. This superfamily of ion channels includes the neuronal nACHR channel, the 5HT3R channel, the GlyR channel and others. However, while GABAA receptor currents are increased by barbiturates (and other general anaesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nACHR channels are blocked by clinically relevant anaesthetic concentrations of both thiopental and pentobarbital. Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.
Barbiturates in overdose with other CNS (central nervous system) depressants for example, alcohol, opiates or benzodiazepines is even more dangerous due to additive CNS and respiratory depressant effects. In the case of benzodiazepines not only do they have additive effects, barbiturates also increase the binding affinity of the benzodiazepine binding site thus leading to an exaggerated effect of benzodiazepines.
Marilyn Monroe and Judy Garland both died of barbiturate overdose.
, barbiturates are intoxicating and produce similar effects during intoxication. The symptoms of barbiturate intoxication include respiratory depression, lowered blood pressure, fatigue, fever, unusual excitement, irritability, dizziness, poor concentration, sedation, confusion, impaired coordination, impaired judgment, addiction, and respiratory arrest, which may lead to death.
Recreational users report that a barbiturate high gives them feelings of relaxed contentment and euphoria
. The main risk of acute barbiturate abuse is respiratory depression. Physical and psychological dependence may also develop with repeated use. Other effects of barbiturate intoxication include drowsiness, lateral and vertical
nystagmus, slurred speech and ataxia
, decreased anxiety, a loss of inhibitions. Barbiturates are also used to alleviate the adverse or withdrawal effects of illicit drug misuse.
Drug users tend to prefer short-acting and intermediate-acting barbiturates. 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.
Slang terms for barbiturates include barbs, bluebirds, blues, dolls, downers, goofballs,Sleepers and tooties .
In the 1950s and 1960s, increasing reports began to be published about barbiturate overdoses
and dependence problems, which eventually led to the scheduling of barbiturates as controlled drugs.
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 amphetamine
s, barbiturates, and other synthetics, the treaty
today regulates secobarbital
, amobarbital
, butalbital
, cyclobarbital
, and pentobarbital
as schedule III, and allobarbital
, methylphenobarbital
, phenobarbital
, and vinylbital
as schedule IV scheduled substances
.
, not for their efficiencies as drugs but for applications in supramolecular chemistry
, in the conception of materials and molecular devices.
Depressant
A depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain...
s, and can therefore produce a wide spectrum of effects, from mild sedation
Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
to total anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
. They are also effective as anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
s, as hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
s, and as anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s. Barbiturates also have analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
effects, however these effects are somewhat weak, preventing barbiturates from being used in surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
in the absence of other analgesics. They have addiction potential, both physical and psychological. Barbiturates have now largely been replaced by benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s in routine medical practice - for example, in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous in overdose
Drug overdose
The term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced...
. However, barbiturates are still used in general anesthesia, for epilepsy, and assisted suicide. Barbiturates are derivatives of barbituric acid
Barbituric acid
Barbituric acid or malonylurea or 6-hydroxyuracil is an organic compound based on a pyrimidine heterocyclic skeleton. It is an odorless powder soluble in water. Barbituric acid is the parent compound of barbiturate drugs, although barbituric acid itself is not pharmacologically active...
.
History
Barbituric acidBarbituric acid
Barbituric acid or malonylurea or 6-hydroxyuracil is an organic compound based on a pyrimidine heterocyclic skeleton. It is an odorless powder soluble in water. Barbituric acid is the parent compound of barbiturate drugs, although barbituric acid itself is not pharmacologically active...
was first synthesized December 6, 1864, by German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
researcher Adolf von Baeyer
Adolf von Baeyer
Johann Friedrich Wilhelm Adolf von Baeyer was a German chemist who synthesized indigo, and was the 1905 recipient of the Nobel Prize in Chemistry. Born in Berlin, he initially studied mathematics and physics at Berlin University before moving to Heidelberg to study chemistry with Robert Bunsen...
. This was done by condensing urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
(an animal waste product) with diethyl malonate
Diethyl malonate
Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes...
(an ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
derived from the acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
of apple
Apple
The apple is the pomaceous fruit of the apple tree, species Malus domestica in the rose family . It is one of the most widely cultivated tree fruits, and the most widely known of the many members of genus Malus that are used by humans. Apple grow on small, deciduous trees that blossom in the spring...
s). 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
Tavern
A tavern is a place of business where people gather to drink alcoholic beverages and be served food, and in some cases, where travelers receive lodging....
where the town's artillery
Artillery
Originally applied to any group of infantry primarily armed with projectile weapons, artillery has over time become limited in meaning to refer only to those engines of war that operate by projection of munitions far beyond the range of effect of personal weapons...
garrison
Garrison
Garrison is the collective term for a body of troops stationed in a particular location, originally to guard it, but now often simply using it as a home base....
were also celebrating the feast of Saint Barbara
Saint Barbara
Saint Barbara, , Feast Day December 4, known in the Eastern Orthodox Church as the Great Martyr Barbara, was an early Christian saint and martyr....
—the patron saint of artillerists. An artillery officer is said to have christened the new substance by amalgamating Barbara with urea. Another story holds that Von Baeyer synthesized the substance from the collected urine of a Munich waitress named Barbara. No substance of medical value was discovered, however, until 1903 when two German scientists working at Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
, Emil Fischer
Franz Joseph Emil Fischer
Franz Joseph Emil Fischer was a German chemist. He and Hans Tropsch discovered the Fischer-Tropsch process. With Hans Schrader he developed the Fischer Assay, a standardized laboratory test for determining the oil yield from oil shale to be expected from a conventional shale oil extraction...
and Joseph von Mering
Joseph von Mering
Josef, Baron von Mering was a German physician.Working at the University of Strasbourg, Mering was the first person to discover that one of the pancreatic functions is the production of insulin, a hormone which controls blood sugar levels.Mering was curious about the...
, discovered that barbital
Barbital
Barbital , also called barbitone, was the first commercially marketed barbiturate. It was used as a sleeping aid from 1903 until the mid-1950s. The chemical names for barbital are diethylmalonyl urea or diethylbarbituric acid...
was very effective in putting dogs to sleep. Barbital was then marketed by Bayer under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
Veronal. It is said that Von Mering proposed this name because the most peaceful place he knew was the Italian
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
city of Verona
Verona
Verona ; German Bern, Dietrichsbern or Welschbern) is a city in the Veneto, northern Italy, with approx. 265,000 inhabitants and one of the seven chef-lieus of the region. It is the second largest city municipality in the region and the third of North-Eastern Italy. The metropolitan area of Verona...
.
It was not until the 1950s that the behavioural disturbances and physical dependence potential of barbiturates became recognized.
While barbituric acid itself does not have any direct effect on the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, chemists have derived over 2,500 compounds from it that possess pharmacologically active qualities. The broad class of barbiturates is further broken down and classified according to speed of onset and duration of action. Ultrashort-acting barbiturates are commonly used for anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
because their extremely short duration of action allows for greater control. These properties allow doctors to rapidly put a patient "under" in emergency surgery situations. Doctors can also bring a patient out of anesthesia just as quickly, should complications arise during surgery. The middle two classes of barbiturates are often combined under the title "short/intermediate-acting." These barbiturates are also employed for anesthetic purposes, and are also sometimes prescribed for anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
or insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. This is not a common practice anymore, however, owing to the dangers of long-term use of barbiturates; they have been replaced by the benzodiazepines for these purposes. The final class of barbiturates are known as long-acting barbiturates (the most notable one being phenobarbital, which has a half-life of roughly 92 hours). This class of barbiturates is used almost exclusively as anticonvulsants, although on rare occasions they are prescribed for daytime sedation. Barbiturates in this class are not used for insomnia, because, owing to their extremely long half-life, patients would awake with a residual "hang-over" effect and feel groggy.
Barbiturates can in most cases be used either as the free acid or as salts of sodium, calcium, potassium, magnesium, lithium, etc. Codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
- and Dionine
Ethylmorphine
Ethylmorphine is an opiate narcotic analgesic .Ethylmorphine was invented in Germany at Merck in 1884 and was used as a weaker alternative to heroin for all indications. Chemically, ethylmorphine is a morphine molecule with a -25 group substituted for the aromatic 3- group...
-based salts of barbituric acid have been developed. In 1912, Bayer introduced another barbituric acid derivative, phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
, under the trade name Luminal
Luminal
Luminal may refer to:* A trade name for the anti-epileptic drug phenobarbital* Luminal , a 2004 film by Italian director Andrea Vecchiato starring Denis Lavant* In biology, pertaining to the lumen, the interior of a hollow structure...
, as a sedative-hypnotic.
Therapeutic uses
Barbiturates like pentobarbitalPentobarbital
Pentobarbital is a short-acting barbiturate that was first synthesized in 1928. Pentobarbital is available as both a free acid and a sodium salt, the former of which is only slightly soluble in water and ethanol....
and phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
were long used as anxiolytics and hypnotics. Today, benzodiazepines have largely supplanted them for these purposes, because benzodiazepines have less potential for lethal overdoses
Drug overdose
The term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced...
.
Other uses related to their physiological properties
Barbiturates in high doses are used for physician-assisted suicide (PAS), and in combination with a muscle relaxantMuscle relaxant
A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics...
for euthanasia
Euthanasia
Euthanasia refers to the practice of intentionally ending a life in order to relieve pain and suffering....
and for capital punishment
Capital punishment
Capital punishment, the death penalty, or execution is the sentence of death upon a person by the state as a punishment for an offence. Crimes that can result in a death penalty are known as capital crimes or capital offences. The term capital originates from the Latin capitalis, literally...
by lethal injection
Lethal injection
Lethal injection is the practice of injecting a person with a fatal dose of drugs for the express purpose of causing the immediate death of the subject. The main application for this procedure is capital punishment, but the term may also be applied in a broad sense to euthanasia and suicide...
.
Thiopental is an ultra-short acting barbiturate that is marketed under the name Sodium Pentothal. It is often mistaken for "Truth Serum" or Sodium Amytal, an intermediate-acting barbiturate that is used for sedation and to treat insomnia, but was also used in so-called Sodium Amytal "interviews" where the person being questioned would be much more likely to provide the truth whilst under the influence of this drug. When dissolved in water, Sodium Amytal can be swallowed, or it can be administered by intravenous injection. The drug does not itself force people to tell the truth, but is thought to decrease inhibitions, making subjects more likely to be caught off guard when questioned.
Mechanism of action
The principal mechanism of action of barbiturates is believed to be their affinity for the GABAA receptor (Acts on GABA : BDZ receptor Cl- channel complex). GABAGabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
is the principal inhibitory neurotransmitter in the mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS). Barbiturates bind to the GABAA receptor at the alpha subunit, which are binding sites distinct from GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
itself and also distinct from the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
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
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
, a subtype of glutamate receptor
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABAA 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.
Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.
Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. This superfamily of ion channels includes the neuronal nACHR channel, the 5HT3R channel, the GlyR channel and others. However, while GABAA receptor currents are increased by barbiturates (and other general anaesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nACHR channels are blocked by clinically relevant anaesthetic concentrations of both thiopental and pentobarbital. Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.
Tolerance, dependence, overdose, and adverse reaction
Older adults and pregnant women and babies should consider the risks associated with barbiturate use. When a person ages, the body becomes less able to rid itself of barbiturates. As a result, people over the age of sixty-five are at higher risk of experiencing the harmful effects of barbiturates, including drug dependence and accidental overdose. When barbiturates are taken during pregnancy, the drug passes through the mother's bloodstream to her fetus. After the baby is born, it may experience withdrawal symptoms and have trouble breathing. In addition, nursing mothers who take barbiturates may transmit the drug to their babies through breast milk.Tolerance and dependence
With regular use, tolerance to the effects of barbiturates develops.Overdose
Symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness, shallow breathing, staggering, and in severe cases coma and death. The lethal dosage of barbiturates varies greatly with tolerance and from one individual to another. The amount of 1 g in dose orally can be highly poisonous with dosages from 2g to 10 g being generally fatal depending on the person tolerance level. Even in inpatient settings, however, the development of tolerance is still a problem, as dangerous and unpleasant withdrawal symptoms can result when the drug is stopped after dependence has developed.Barbiturates in overdose with other CNS (central nervous system) depressants for example, alcohol, opiates or benzodiazepines is even more dangerous due to additive CNS and respiratory depressant effects. In the case of benzodiazepines not only do they have additive effects, barbiturates also increase the binding affinity of the benzodiazepine binding site thus leading to an exaggerated effect of benzodiazepines.
Marilyn Monroe and Judy Garland both died of barbiturate overdose.
Adverse reaction
A rare adverse reaction to barbiturates is Stevens–Johnson syndrome, which primarily affects the mucous membranes.Recreational use
Like ethanolEthanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, barbiturates are intoxicating and produce similar effects during intoxication. The symptoms of barbiturate intoxication include respiratory depression, lowered blood pressure, fatigue, fever, unusual excitement, irritability, dizziness, poor concentration, sedation, confusion, impaired coordination, impaired judgment, addiction, and respiratory arrest, which may lead to death.
Recreational users report that a barbiturate high gives them feelings of relaxed contentment and euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
. The main risk of acute barbiturate abuse is respiratory depression. Physical and psychological dependence may also develop with repeated use. Other effects of barbiturate intoxication include drowsiness, lateral and vertical
Vertical direction
In astronomy, geography, geometry and related sciences and contexts, a direction passing by a given point is said to be vertical if it is locally aligned with the gradient of the gravity field, i.e., with the direction of the gravitational force at that point...
nystagmus, slurred speech and ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, decreased anxiety, a loss of inhibitions. Barbiturates are also used to alleviate the adverse or withdrawal effects of illicit drug misuse.
Drug users tend to prefer short-acting and intermediate-acting barbiturates. The most commonly abused are amobarbital
Amobarbital
Amobarbital is a drug that is a barbiturate derivative. It has sedative-hypnotic and analgesic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923...
(Amytal), pentobarbital
Pentobarbital
Pentobarbital is a short-acting barbiturate that was first synthesized in 1928. Pentobarbital is available as both a free acid and a sodium salt, the former of which is only slightly soluble in water and ethanol....
(Nembutal), and secobarbital
Secobarbital
Secobarbital sodium is a barbiturate derivative drug that was first synthesized in 1928 in Germany. It possesses anaesthetic, anticonvulsant, sedative and hypnotic properties...
(Seconal). A combination of amobarbital and secobarbital (called Tuinal
Tuinal
Tuinal is the brand name of a combination drug composed of two barbiturate salts in equal proportions....
) 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
Animal euthanasia
Animal euthanasia is the act of putting to death painlessly or allowing to die, as by withholding extreme medical measures, an animal suffering from an incurable, especially a painful, disease or condition. Euthanasia methods are designed to cause minimal pain and distress...
animals.
Slang terms for barbiturates include barbs, bluebirds, blues, dolls, downers, goofballs,Sleepers and tooties .
Legal status
In the 1940s, military personnel were given "Goofballs" during WWII in the South Pacific region to allow soldiers to tolerate the heat and humidity of daily working conditions. Goofballs were distributed to lower the respiratory system and blood pressure to combat the extreme conditions. Many soldiers returned with addictions that required several months of rehabilitation before discharge. This led to addiction problems through the 1950s and 1960s.In the 1950s and 1960s, increasing reports began to be published about barbiturate overdoses
Drug overdose
The term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced...
and dependence problems, which eventually led to the scheduling of barbiturates as controlled drugs.
In 1970, several barbiturates were designated in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
as controlled substances with the passage of the American Controlled Substances Act
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
of 1970. Pentobarbital
Pentobarbital
Pentobarbital is a short-acting barbiturate that was first synthesized in 1928. Pentobarbital is available as both a free acid and a sodium salt, the former of which is only slightly soluble in water and ethanol....
, secobarbital
Secobarbital
Secobarbital sodium is a barbiturate derivative drug that was first synthesized in 1928 in Germany. It possesses anaesthetic, anticonvulsant, sedative and hypnotic properties...
and amobarbital
Amobarbital
Amobarbital is a drug that is a barbiturate derivative. It has sedative-hypnotic and analgesic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923...
were designated schedule II drugs, butabarbital
Butabarbital
Butabarbital is a prescription barbiturate sleep aid. Butabarbital has a particularly fast onset of effects and short duration of action compared to other barbiturates, which makes it useful for certain applications such as treating severe insomnia and relieving anxiety before surgical procedures;...
schedule III, and barbital and phenobarbital schedule IV.
In 1971, the Convention on Psychotropic Substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
was signed in Vienna
Vienna
Vienna is the capital and largest city of the Republic of Austria and one of the nine states of Austria. Vienna is Austria's primary city, with a population of about 1.723 million , and is by far the largest city in Austria, as well as its cultural, economic, and political centre...
. Designed to regulate amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
s, barbiturates, and other synthetics, the treaty
Treaty
A treaty is an express agreement under international law entered into by actors in international law, namely sovereign states and international organizations. A treaty may also be known as an agreement, protocol, covenant, convention or exchange of letters, among other terms...
today regulates secobarbital
Secobarbital
Secobarbital sodium is a barbiturate derivative drug that was first synthesized in 1928 in Germany. It possesses anaesthetic, anticonvulsant, sedative and hypnotic properties...
, amobarbital
Amobarbital
Amobarbital is a drug that is a barbiturate derivative. It has sedative-hypnotic and analgesic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923...
, butalbital
Butalbital
Butalbital, structure presents as 5-allyl-5-isobutylbarbituric acid, is a barbiturate with an intermediate duration of action. It has the same chemical formula as talbutal but a different structure. Butalbital is often combined with other medications, such as paracetamol or aspirin, and is...
, cyclobarbital
Cyclobarbital
Cyclobarbital, also known as cyclobarbitol or cyclobarbitone, is a drug which is a barbiturate derivative....
, and pentobarbital
Pentobarbital
Pentobarbital is a short-acting barbiturate that was first synthesized in 1928. Pentobarbital is available as both a free acid and a sodium salt, the former of which is only slightly soluble in water and ethanol....
as schedule III, and allobarbital
Allobarbital
Allobarbital is a barbiturate derivative invented in 1912 by Ernst Preiswerk and Ernst Grether working for CIBA. It was used primarily as an anticonvulsant although it has now largely been replaced by newer drugs with improved safety profiles...
, methylphenobarbital
Methylphenobarbital
Methylphenobarbital , also known as mephobarbital and mephobarbitone , marketed under brand names such as Mebaral, Mephyltaletten, Phemiton, and Prominal, is a drug which is a barbiturate derivative and is used primarily as an anticonvulsant, but also as a sedative and anxiolytic...
, phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
, and vinylbital
Vinylbital
Vinylbital, also known as butylvinyl, is a drug which is a barbiturate derivative. It possesses sedative properties....
as schedule IV scheduled substances
Convention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
.
Other uses in chemistry
In 1988, the synthesis and binding studies of an artificial receptor binding barbiturates by 6 complementary hydrogen bonds was published. Since this first article, different kind of receptors were designed, as well as different barbiturates and cyanuratesCyanuric acid
Cyanuric acid or 1,3,5-triazine-2,4,6-triol is a chemical compound with the formula 3. Like many industrially useful chemicals, this triazine has many synonyms. This white, odorless solid finds use as a precursor or a component of bleaches, disinfectants, and herbicides...
, not for their efficiencies as drugs but for applications in supramolecular chemistry
Supramolecular chemistry
Supramolecular chemistry refers to the area of chemistry beyond the molecules and focuses on the chemical systems made up of a discrete number of assembled molecular subunits or components...
, in the conception of materials and molecular devices.
Examples
| Short Name | R1 | R2 | IUPAC Name |
|---|---|---|---|
| Allobarbital Allobarbital Allobarbital is a barbiturate derivative invented in 1912 by Ernst Preiswerk and Ernst Grether working for CIBA. It was used primarily as an anticonvulsant although it has now largely been replaced by newer drugs with improved safety profiles... |
CH2CHCH2 Allyl An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl... |
CH2CHCH2 Allyl An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl... |
5,5-diallylbarbiturate |
| Amobarbital Amobarbital Amobarbital is a drug that is a barbiturate derivative. It has sedative-hypnotic and analgesic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923... |
CH2CH3 Ethyl group In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5.... |
CH2CH2CH(CH3)2 | 5-ethyl-5-isopentyl-barbiturate |
| Aprobarbital Aprobarbital Aprobarbital is a barbiturate derivative invented in the 1920s by Ernst Preiswerk. It has sedative, hypnotic and anticonvulsant properties, and was used primarily for the treatment of insomnia... |
CH2CHCH2 Allyl An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl... |
CH(CH3)2 Isopropyl In organic chemistry, isopropyl is a propyl with a group attached to the secondary carbon. If viewed as a functional group an isopropyl is an organic compound with a propyl group attached at its secondary carbon.The bond is therefore on the middle carbon.... |
5-allyl-5-isopropyl-barbiturate |
| Alphenal Alphenal Alphenal is a barbiturate derivative invented in the 1960s. It has primarily anticonvulsant properties, and was used occasionally for the treatment of epilepsy or convulsions, although not as commonly as better known barbiturates such as phenobarbital.... |
CH2CHCH2 Allyl An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl... |
C6H5 | 5-allyl-5-phenyl-barbiturate |
| Barbital Barbital Barbital , also called barbitone, was the first commercially marketed barbiturate. It was used as a sleeping aid from 1903 until the mid-1950s. The chemical names for barbital are diethylmalonyl urea or diethylbarbituric acid... |
CH2CH3 Ethyl group In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5.... |
CH2CH3 Ethyl group In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5.... |
5,5-diethylbarbiturate |
| Brallobarbital Brallobarbital Brallobarbital is a barbiturate derivative invented in 1964. It has sedative and hypnotic properties, and was used for the treatment of insomnia. Brallobarbital was primarily sold as part of a combination product called Vesparax, composed of 150 mg secobarbital, 50 mg brallobarbital and 50 mg... |
CH2CHCH2 Allyl An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl... |
CH2CBrCH2 Allyl An allyl group is a substituent with the structural formula H2C=CH-CH2R, where R is the connection to the rest of the molecule. It is made up of a methylene , attached to a vinyl group . The name is derived from the Latin word for garlic, Allium sativum. Theodor Wertheim isolated an allyl... |
5-allyl-5-(2-bromo-allyl)-barbiturate |
| Phenobarbital Phenobarbital Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the... |
CH2CH3 Ethyl group In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5.... |
C6H5 | 5-ethyl-5-phenylbarbiturate |
External links
- U.S. Drug Enforcement Administration Source for some public domain text used on this page.
- History of Barbiturates