Barbiturates are drugs A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease that act as central nervous system depressants Depressants are psychoactive drugs which temporarily diminish the function or activity of a specific part of the body or mind. Examples of these kinds of effects may include anxiolysis, sedation, and hypotension. Due to their effects typically having a "down" quality to them, depressants are also occasionally referred to as "downers&, and, by virtue of this, they produce a wide spectrum of effects, from mild sedation Sedation is a medical procedure involving the administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Drugs which can be used for sedation include propofol, etomidate, ketamine, fentanyl and midazolam to total anesthesia Anesthesia, or anaesthesia , has traditionally meant the condition of having sensation (including the feeling of pain) blocked or temporarily taken away. It is a pharmacologically induced reversible state of amnesia, analgesia, loss of responsiveness, loss of skeletal muscle reflexes and/or decreased stress response. This allows patients to. They are also effective as anxiolytics An anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders, as hypnotics 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. When used in anesthesia to produce and maintain unconsciousness "sleep" is metaphorical and there are no regular sleep stages or cyclical natural states; patients rarely recover, and as anticonvulsants 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. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neurons that start a seizure. They have addiction potential, both physical and psychological. Barbiturates have now largely been replaced by benzodiazepines A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and made available in 1960 by Hoffmann–La Roche, which has also marketed diazepam (Valium) since 1963 in routine medical practice - for example, in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous in overdose The term drug overdose describes the ingestion or application of a drug or other substance in quantities that are excessive. An overdose is widely considered harmful and dangerous as it can result in death. However, barbiturates are still used in general anesthesia, as well as for epilepsy. Barbiturates are derivatives of 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 hot water. Barbituric acid is the parent compound of barbiturate drugs, although barbituric acid itself is not pharmacologically active. The compound was discovered by the German chemist Adolf.

History

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 hot water. Barbituric acid is the parent compound of barbiturate drugs, although barbituric acid itself is not pharmacologically active. The compound was discovered by the German chemist Adolf was first synthesized December 6, 1864, by German A region named Germania, inhabited by several Germanic peoples, has been known and documented before AD 100. Beginning in the 10th century, German territories formed a central part of the Holy Roman Empire, which lasted until 1806. During the 16th century, northern Germany became the centre of the Protestant Reformation. As a modern nation-state, researcher 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. There he worked primarily in August Kekulé's. This was done by condensing urea Urea or carbamide is an organic compound with the chemical formula (N (an animal waste product) with diethyl malonate Malonic acid is a dicarboxylic acid with structure C (an 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 (hydroxyl) group is replaced by an -O-alkyl (alkoxy) group, and most commonly from carboxylic acids and alcohols. Basically, esters are derived from the acid An acid is any chemical compound that, when dissolved in water, gives a solution with a hydrogen ion activity greater than in pure water, i.e. a pH less than 7.0 in its standard state. That approximates the modern definition of Johannes Nicolaus Brønsted and Martin Lowry, who independently defined an acid as a compound which donates a hydrogen of apples The apple is the pomaceous fruit of the apple tree, species Malus domestica in the rose family and is a perennial. 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). 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 A tavern is a place of business where people gather to drink alcoholic beverages and, more than likely, also be served food. An Inn is a tavern which has a license to put up guests. The word derives from the Latin taberna and the Greek ταβέρνα/taverna, whose original meaning was a shed or workshop. The distinction of a tavern from an inn, where the town's artillery Originally applied to any group of infantry primarily armed with mechanical 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. These engines comprise specialised devices which use some form of stored garrison Garrison (from the French garnison, itself from the verb garnir, "to equip") 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. The garrison is usually a city, town, fort, castle or similar. For example, the 1st Battalion, 1st Infantry (U.S were also celebrating the feast of Saint Barbara Saint Barbara , known in the Eastern Orthodox Church as the Great Martyr Barbara (3rd century - December 4, 306), was a Christian saint and martyr. Although there is no reference to her in the authentic early Christian writings, nor in the original recension of Saint Jerome's martyrology, veneration of her was common from the seventh century — the patron saint of artillerists. An artillery officer is said to have christened the new substance by amalgamating Barbara with urea.^[1] No substance of medical value was discovered, however, until 1903 when two German chemists working at Bayer Bayer AG (FWB: BAYN, TYO: 4863) is a chemical and pharmaceutical company founded in Barmen, Germany in 1863. Today it is headquartered in Leverkusen, North Rhine-Westphalia, Germany. It is well-known for its original brand of aspirin, Emil Fischer and Joseph von Mering, discovered that barbital Barbital , also called barbitone, was the first commercially marketed barbiturate. It was used as a sleeping aid (hypnotic) from 1903 until the mid-1950s. The chemical names for barbital are diethylmalonyl urea or diethylbarbituric acid. Veronal was prepared by condensing diethylmalonic ester with urea in the presence of sodium ethylate, or by was very effective in putting dogs to sleep. Barbital was then marketed by Bayer under the 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 (pronounced /ˈɪtəli/ ; Italian: Italia [iˈtaːlja]), officially the Italian Republic (Italian: Repubblica italiana), is a country located partly on the European Continent and partly on the Italian Peninsula in Southern Europe and on the two largest islands in the Mediterranean Sea, Sicily and Sardinia. Italy shares its northern, Alpine city of Verona Verona listen (Italian pronunciation: [veˈro(ː)na]) is a city in Veneto, northern Italy, home to approx. 265,000 inhabitants and one of the seven provincial capitals of the region. It is the second most populated municipality of the region and the third of North-East Italy. The metro area of Verona has an area of 1.426 km2 (0.55 sq mi) and has a.^[1] It was not until the 1950s that the behavioural disturbances and physical dependence potential of barbiturates became recognised.^[2]

While barbituric acid itself does not have any effect on the central nervous system, to date, chemists have derived over 2,500 compounds that do possess pharmacologically active qualities. The broad class of barbiturates is broken down further 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 Codeine or methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties- and Dionine Ethylmorphine is an opiate narcotic analgesic (pain killer)-based salts of barbituric acid have been developed. In 1912, Bayer introduced another barbituric acid derivative, phenobarbital Phenobarbital or phenobarbitone (former BAN) 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 benzodiazepines for these indications, under the trade name Luminal, as a sedative-hypnotic.^[3]

Therapeutic uses

Barbiturates like 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. One trade name for this drug is Nembutal, coined by Dr. John S. Lundy, who started using it in 1930, from the structural formula of the and phenobarbital Phenobarbital or phenobarbitone (former BAN) 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 benzodiazepines for these indications were long used as anxiolytics An anxiolytic is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders and hypnotics 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. When used in anesthesia to produce and maintain unconsciousness, "sleep" is metaphorical and there are no regular sleep stages or cyclical natural states when used in anesthesia;. Today, benzodiazepines A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and made available in 1960 by Hoffmann–La Roche, which has also marketed diazepam (Valium) since 1963 have largely supplanted them for these purposes, because benzodiazepines have less potential for lethal overdoses The term drug overdose describes the ingestion or application of a drug or other substance in quantities that are excessive. An overdose is widely considered harmful and dangerous as it can result in death.^[4][5][6]

Barbiturates are classified as ultrashort-, short-, intermediate-, and long-acting, depending on how quickly they act and how long their effects last.^[7] Barbiturates are still widely used in surgical Surgery is a 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, to help improve bodily function or appearance, and sometimes for religious reasons. An act of performing surgery may be called a surgical procedure, operation, or simply anesthesia Anesthesia, or anaesthesia , has traditionally meant the condition of having sensation (including the feeling of pain) blocked or temporarily taken away. It is a pharmacologically induced reversible state of amnesia, analgesia, loss of responsiveness, loss of skeletal muscle reflexes and/or decreased stress response. This allows patients to, especially to induce anesthesia, though their use during induction of anesthesia has largely been supplanted by propofol Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine. Propofol is approved for use in more than 50 countries, and generic versions are. Ultrashort barbiturates such as thiopental Sodium thiopental, better known as Sodium Pentothal , thiopental, thiopentone sodium, or Trapanal (also a trademark), is a rapid-onset short-acting barbiturate general anaesthetic. Sodium thiopental is a depressant and is sometimes used during interrogations – not to cause pain (in fact, it may have just the opposite effect), but to weaken the (Pentothal) produce unconsciousness within about a minute of intravenous (IV) injection. These drugs are used to prepare patients for surgery; other general anesthetics A general anaesthetic drug is an anaesthetic drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anesthesia provider in order to induce or maintain general anaesthesia to facilitate surgery like sevoflurane Sevoflurane , also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, non-flammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology[citation needed]. It is often administered in a mixture or isoflurane Isoflurane (2-chloro-2--1,1,1-trifluoro-ethane) is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its use in human medicine is now starting to decline, being replaced with sevoflurane, desflurane and the intravenous anaesthetic are then used to keep the patient from waking up before the surgery is complete. Because thiopental and other ultrashort-acting barbiturates are typically used in hospital settings, they are not very likely to be abused, noted the DEA.^[8]

Phenobarbital Phenobarbital or phenobarbitone (former BAN) 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 benzodiazepines for these indications is used as an 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. The goal of an anticonvulsant is to suppress the rapid and excessive firing of neurons that start a seizure for people suffering from seizure An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness. It can manifest as an alteration in mental state, tonic or clonic disorders such as febrile seizures A febrile seizure, also known as a fever fit or febrile convulsion is a convulsion triggered by a rise in body temperature. They most commonly occur in children between the ages of 6 months and 3 years and are twice as common in boys than girls. The direct cause of a febrile seizure is not known; however, it is normally precipitated by a recent, tonic-clonic seizures Tonic–clonic seizures are a type of generalized seizure that affects the entire brain. Tonic–clonic seizures are the seizure type most commonly associated with epilepsy and seizures in general, though it is a misconception that they are the only type. (See seizure types), status epilepticus Status epilepticus is a life-threatening condition in which the brain is in a state of persistent seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting longer than 30 minutes , or recurrent seizures without regaining consciousness between seizures for greater than 30 minutes (or shorter with, and eclampsia Eclampsia , an acute and life-threatening complication of pregnancy, is characterized by the appearance of tonic-clonic seizures, usually in a patient who had developed preeclampsia. (Preeclampsia and eclampsia are collectively called Hypertensive disorder of pregnancy and toxemia of pregnancy.).^[9]

Long-acting barbiturates such as phenobarbital (Luminal) and mephobarbital (Mebaral) are prescribed for few reasons. When taken at bedtime, they help treat insomnia, and when taken during the day they have sedative effects that can aid in the treatment of tension and anxiety. However, prescription for the treatment of these conditions is now rare due to the risks of physical dependence and fatal overdose. These drugs are more often prescribed 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.^[10] Long-acting barbiturates take effect within one to two hours and last 12 hours or longer.^[8]

Other uses related to their physiological properties

Barbiturates in high doses are used for physician-assisted suicide (PAS), and in combination with a muscle relaxant for euthanasia and for capital punishment by lethal injection.^[11][12] Thiopental, an ultra-short acting barbiturate that is marketed under the name Sodium Pentothal, is sometimes used as a "truth serum". When dissolved in water, it can be swallowed or 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.^[13]

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 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 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.^[9] Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABA_A receptor (pharmacodynamics: this increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABA_A 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.^[14][15]

Further, barbiturates are relatively "promiscious" (i.e. non-selective) compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABA_A 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. Surprisingly, while GABA_A 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.^[16] 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.^[17]

Tolerance, dependence and overdose

Older adults and pregnant women 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.^[18] 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.^[19]

Tolerance and dependence

With regular use tolerance to the effects of barbiturates develops.

Overdose

Recreational use

Like ethanol, 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.^[20]

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.^[21] 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.^[22][23]

Drug users tend to prefer short-acting and intermediate-acting barbiturates.^[24] 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.^[8]

Slang terms for barbiturates include barbs, bluebirds, blues, dolls, downers, goofballs and tooties .^[25]

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 cause several months of rehabilitation before being discharged. This led to addiction problems through the 1950s and 1960s.

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 amphetamines, 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.

Other uses in chemistry

In 1988, the synthesis and binding studies of an artificial receptor binding barbiturates by 6 complementary hydrogen bonds was published.^[26] Since this first article, different kind of receptors were designed, as well as different barbiturates and cyanurates, not for their efficiencies as drugs but for applications in supramolecular chemistry, in the conception of materials and molecular devices.

Examples

See also

• Benzodiazepines

References

1. ^ ^{a b} "Barbiturates". http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/barbiturate_text.htm. Retrieved 2007-10-31.
2. ^ Galanter, Marc; Kleber, Herbert D. (1 July 2008). The American Psychiatric Publishing Textbook of Substance Abuse Treatment (4th ed.). United States of America: American Psychiatric Publishing Inc. p. 217. ISBN 978-1585622764. http://books.google.com/?id=6wdJgejlQzYC.
3. ^ Sneader, Walter (2005-06-23). Drug Discovery. John Wiley and Sons. pp. 369. ISBN 0-471-89979-8.
4. ^ Whitlock FA (June 14, 1975). "Suicide in Brisbane, 1956 to 1973: the drug-death epidemic". Med J Aust 1 (24): 737–43. PMID 239307.
5. ^ Johns MW (1975). "Sleep and hypnotic drugs". Drugs 9 (6): 448–78. doi:10.2165/00003495-197509060-00004. PMID 238826.
6. ^ Jufe GS (Jul-August 2007). "[New hypnotics: perspectives from sleep physiology]". Vertex 18 (74): 294–9. PMID 18265473.
7. ^ "Barbiturates: How Is It Taken?". azdrugs.org. 2005–2007. http://azdrugs.org/barbiturates/how-taken. Retrieved 2007-10-31.
8. ^ ^{a b c} DEA Brief on Barbiturates
9. ^ ^{a b} Brunton, Laurence L.; Lazo, John S.; Parker, Keith L.; Goodman, Louis Sanford; Gilman, Alfred Goodman (2005). Goodman & Gilman's Pharmacological Basis of Therapeutics. McGraw-Hill. ISBN 0071422803.
10. ^ Kosten TR, O'Connor PG. "Management of drug and alcohol withdrawal." New England Journal of Medicine. 1 May 2003;348(18):1786-95. PMID 12724485
11. ^ "Administration and Compounding Of Euthanasic Agents". http://www.wweek.com/html/euthanasics.html. Retrieved 15 July 2008.
12. ^ Daniel Engber. "Why do lethal injections have three drugs?". Slate Magazine. http://www.slate.com/id/2141000/. Retrieved 15 July 2008.
13. ^ "Neuroscience for Kids - Barbiturates". http://faculty.washington.edu/chudler/barb.html. Retrieved 2008-06-02.
14. ^ Neil Harrison; Wallace B Mendelson and Harriet de Wit (2000). "Barbiturates". Neuropsychopharmacology. http://www.acnp.org/g4/GN401000173/CH169.html. Retrieved 15 July 2008.
15. ^ Society for Neurochemistry, American; George J. Siegel M.D., Bernard W. Agranoff M.D., Stephen K. Fisher Ph.D., R. Wayne Albers Ph.D., Michael D. Uhler Ph.D. (1999) [1998]. "Part 2 Chapter 16". Basic Neurochemistry - Molecular, Cellular and Medical Aspects (Sixth ed.). Lippincott Williams and Wilkins. ISBN 0-397-51820-X. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.1181. Retrieved July 2008.
16. ^ Weber, M; Motin, L; Gaul, S; Beker, F; Fink, RH; Adams, DJ (January 2005). "Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons.". British Journal of Pharmacology 144 (1): 98–107. doi:10.1038/sj.bjp.0705942. PMID 15644873.
17. ^ Franks, NP; Lieb, WR (23 November 1998). "Which molecular targets are most relevant to general anaesthesia?". Toxicology Letters 100–101: 1–8. doi:10.1016/S0378-4274(98)00158-1. PMID 10049127.
18. ^ WebMD. "Toxicity, Barbiturate". eMedicine. http://www.emedicine.com/MED/topic207.htm. Retrieved 15 July 2008.
19. ^ Nau H; Kuhnz W, Egger HJ, Rating D, Helge H (Nov-December 1982). "Anticonvulsants during pregnancy and lactation. Transplacental, maternal and neonatal pharmacokinetics". Clin Pharmacokinet 7 (6): 508–43. doi:10.2165/00003088-198207060-00003. PMID 6819105.
20. ^ National Institute on Drug Abuse. "Commonly Abused Drugs". pp. 1. http://www.drugabuse.gov/DrugPages/DrugsofAbuse.html. Retrieved 15 July 2008.
21. ^ Schlatter J; Sitbon N, Saulnier JL (February 17, 2001). "[Drugs and drug abusers]". Presse Med 30 (6): 282–7. PMID 11252979.
22. ^ Emedicine Health. "Barbiturate Abuse". pp. 1. http://www.emedicinehealth.com/barbiturate_abuse/article_em.htm. Retrieved 15 July 2008.
23. ^ Faulkner TP; Hayden JH, Mehta CM, Olson DA, Comstock EG (1979). "Dose-response studies on tolerance to multiple doses of secobarbital and methaqualone in a polydrug abuse population". Clin Toxicol 15 (1): 23–37. doi:10.3109/15563657908992476. PMID 498734.
24. ^ Coupey SM. "Barbiturates." Pediatrics in Review. 1997 Aug;18(8):260-4. PMID 9255991
25. ^ Hamid H.; El-Mallakh RS, Vandeveir K (March 2005). "Substance Abuse: Medical and Slang Terminology". South Med J (Medscape) 98 (3): 350–362. doi:10.1097/01.SMJ.0000153639.23135.6A. PMID 15813163. http://www.medscape.com/viewarticle/501975_4.
26. ^ Chang, S.-K.; Hamilton, A. D. Journal of the American Chemical Society 1988, 110, 1318-1319.

External links

• U.S. Drug Enforcement Administration Source for some public domain text used on this page.
• History of Barbiturates

Categories: Barbiturates | German inventions

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