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A barbiturate[note 1][1] is a drug that acts as a central nervous system depressant, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, hypnotics, and anticonvulsants. Barbiturates have addiction potential, both physical and psychological. They have largely been replaced by benzodiazepines in routine medical practice, particularly in the treatment of anxiety and insomnia, due to the significantly lower risk of overdose and the lack of an antidote for barbiturate overdose. Despite this, barbiturates are still in use for various purposes: in general anesthesia, epilepsy, treatment of acute migraines or cluster headaches, euthanasia, capital punishment, and assisted suicide.[2] The name barbiturate originates from the fact that they are all chemical derivatives of barbituric acid.[3]

Contents

1 Medical uses 2 Other uses 3 Side effects

3.1 Tolerance and dependence

4 Overdose 5 Mechanism of action 6 History 7 Society and culture

7.1 Legal status 7.2 Recreational use

8 Other uses in chemistry 9 Examples 10 See also 11 References 12 External links

Medical uses[edit] Barbiturates
Barbiturates
such as phenobarbital were long used as anxiolytics and hypnotics, but today have been largely replaced by benzodiazepines for these purposes because the latter are less toxic in overdose.[4][5][6] However, barbiturates are still used as anticonvulsants (e.g., phenobarbital and primidone) and general anesthetics (e.g., sodium thiopental). Other uses[edit] Barbiturates
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.[7][8] Barbiturates
Barbiturates
are frequently employed as euthanizing agents in small-animal veterinary medicine. Thiopental
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 and slow creative thinking, making subjects more likely to be caught off guard when questioned, and increasing the possibility of the subject revealing information through emotional outbursts.[9] The memory-impairing effects and cognitive impairments induced by the drug are thought to reduce a subject's ability to invent and remember lies. This practice is no longer considered legally admissible in court due to findings that subjects undergoing such interrogations may form false memories, putting the reliability of all information obtained through such methods into question. Nonetheless, it is still employed in certain circumstances by defense and law enforcement agencies as a "humane" alternative to torture interrogation when the subject is believed to have information critical to the security of the state or agency employing the tactic.[10] Side effects[edit]

Addiction
Addiction
experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Barbiturates were ranked 5th in dependence, 3rd in physical harm, and 4th in social harm.[11]

There are special risks to consider for older adults, women who are pregnant, and babies. 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.[12] When barbiturates are taken during pregnancy, the drug passes through the placenta to the 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.[13] A rare adverse reaction to barbiturates is Stevens-Johnson syndrome, which primarily affects the mucous membranes. Tolerance and dependence[edit] Main article: Barbiturate
Barbiturate
dependence With regular use, tolerance to the effects of barbiturates develops. Research shows that tolerance can develop with even one administration of a barbiturate. As with all GABAergic drugs barbiturate withdrawal produces potentially fatal effects such as seizures in a manner reminiscent of delirium tremens and benzodiazepine withdrawal although its more direct mechanism of GABA
GABA
agonism makes barbiturate withdrawal more severe than that of alcohol or benzodiazepines (subsequently making it one of the most dangerous withdrawals of any known addictive substance). Similar to benzodiazepines the longer acting barbiturates produce a less severe withdrawal syndrome than short acting and ultra short acting barbiturates. Withdrawal symptoms are dose-dependent with heavier users being affected worse than lower-dose addicts. The pharmacological treatment of barbiturate withdrawal is an extended process often consisting of converting the patient to a long acting benzodiazepine (i.e. Valium), followed by slowly tapering off the benzodiazepine. Mental cravings for barbiturates can last for months or years in some cases and counselling/support groups are highly encouraged by addiction specialists. Patients should never try to tackle the task of discontinuing barbiturates without consulting a doctor due to the high lethality and relatively sudden onset of the withdrawal, attempting to quit "cold turkey" may result in serious neurological damage, severe physical injuries received during convulsions, and even death via glutamatergic excitotoxicity. Overdose[edit] Main article: Barbiturate
Barbiturate
overdose Some symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgement, drowsiness, shallow breathing, staggering, and, in severe cases, coma or death. The lethal dosage of barbiturates varies greatly with tolerance and from one individual to another. The lethal dose is highly variable among different members of the class with superpotent barbiturates such as pentobarbital being potentially fatal in considerably lower doses than the low-potency barbiturates such as butalbital. 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. Tolerance to the anxiolytic and sedative effects of barbiturates tends to develop faster than tolerance to their effects on smooth muscle, respiration, and heart rate, making them generally unsuitable for a long time psychiatric use. Tolerance to the anticonvulsant effects tends to correlate more with tolerance to physiological effects, however, meaning that they are still a viable option for long-term epilepsy treatment. Barbiturates
Barbiturates
in overdose with other CNS (central nervous system) depressants (e.g. alcohol, opiates, benzodiazepines) are 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, leading to exaggerated benzodiazepine effects. (ex. If a benzodiazepine increases the frequency of channel opening by 300%, and a barbiturate increases the duration of their opening by 300%, then the combined effects of the drugs increase the channels overall function by 900%, not 600%). The longest-acting barbiturates have half-lives of a day or more, and subsequently result in bioaccumulation of the drug in the system. The therapeutic and recreational effects of long-acting barbiturates wear off significantly faster than the drug can be eliminated, allowing the drug to reach toxic concentrations in the blood following repeated administration (even when taken at the therapeutic/prescribed dose) despite the user feeling little or no effects from the plasma-bound concentrations of the drug. Users who consume alcohol or other sedatives after the drugs effects have worn but before it has cleared the system may experience a greatly exaggerated effect from the other sedatives which can be incapacitating or even fatal. Barbiturates
Barbiturates
induce a number of hepatic CYP enzymes (most notably CYP2C9, CYP2C19
CYP2C19
and CYP3A4),[14] leading to exaggerated effects from many prodrugs and decreased effects from drugs which are metabolized by these enzymes to inactive metabolites. This can result in fatal overdoses from drugs such as codeine, tramadol, and carisoprodol, which become considerably more potent after being metabolized by CYP enzymes. Although all known members of the class possess relevant enzyme induction capabilities the degree of inhibition overall as well as the impact on each specific enzyme span a broad range with phenobarbital and secobarbital being the most potent enzyme inducers and butalbital and talbutal being among the weakest enzyme inducers in the class. People who are known to have killed themselves with a barbiturate overdose include Charles Boyer, Dalida, Phyllis Hyman, Lupe Velez, Carole Landis, Jean Seberg, Abbie Hoffman, Felix Hausdorff
Felix Hausdorff
and C. P. Ramanujam. Others who have died as a result of barbiturate overdose include Judy Garland, Marilyn Monroe, Ellen Wilkinson, Dorothy Kilgallen, Pier Angeli, Brian Epstein, Alan Wilson, Jimi Hendrix, Edie Sedgwick, Inger Stevens
Inger Stevens
and Kenneth Williams; in some cases these have been speculated to be suicides as well. Dorothy Dandridge
Dorothy Dandridge
died of either an overdose or an unrelated embolism. Ingeborg Bachmann
Ingeborg Bachmann
may have died of the consequences of barbiturate withdrawal. Mechanism of action[edit] Barbiturates
Barbiturates
act as positive allosteric modulators, and at higher doses, as agonists of GABAA
GABAA
receptors.[15] GABA
GABA
is the principal inhibitory neurotransmitter in the mammalian central nervous system (CNS). Barbiturates
Barbiturates
bind to the GABAA
GABAA
receptor at multiple homologous transmembrane pockets located at subunit interfaces,[16] which are binding sites distinct from GABA
GABA
itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA
GABA
at this receptor. In addition to this GABAergic effect, barbiturates also block AMPA
AMPA
and kainate receptors, subtypes of ionotropic glutamate receptor. Glutamate
Glutamate
is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABAA
GABAA
receptors and inhibit excitatory AMPA
AMPA
receptors can explain the superior CNS-depressant effects of these agents to alternative GABA potentiating agents such as benzodiazepines and quinazolinones. At higher concentration, they inhibit the Ca2+-dependent release of neurotransmitters such as glutamate via an effect on P/Q-type voltage-dependent calcium channels.[17] Barbiturates
Barbiturates
produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA
GABAA
receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA
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.[18][19] Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA
GABAA
receptor channel is only one of several representatives. This superfamily of ion channels includes the neuronal nACh receptor channel, the 5-HT3 receptor
5-HT3 receptor
channel, and the glycine receptor channel. However, while GABAA
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.[20] 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.[21] This is the mechanism responsible for the (mild to moderate) anesthetic effect of barbiturates in high doses when used in anesthetic concentration. History[edit] Barbituric acid
Barbituric acid
was first synthesized November 27, 1864, by German chemist 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 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 artillerymen. An artillery officer is said to have christened the new substance by amalgamating Barbara with urea.[22] Another story holds that Baeyer synthesized the substance from the collected urine of a Munich waitress named Barbara.[23] 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
Barbital
was then marketed by Bayer
Bayer
under the trade name Veronal. It is said that Mering proposed this name because the most peaceful place he knew was the Italian city of Verona.[22] It was not until the 1950s that the behavioural disturbances and physical dependence potential of barbiturates became recognized.[24] Barbituric acid
Barbituric acid
itself does not have any direct effect on the central nervous system and 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
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
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
Bayer
introduced another barbituric acid derivative, phenobarbital, under the trade name Luminal, as a sedative-hypnotic.[25] Society and culture[edit] Legal status[edit] During World War II, military personnel in the Pacific region were given "goofballs" to allow them to tolerate the heat and humidity of daily working conditions. Goofballs were distributed to reduce the demand on the respiratory system, as well as maintaining blood pressure, to combat the extreme conditions. Many soldiers returned with addictions that required several months of rehabilitation before discharge. This led to growing dependency problems, often exacerbated by indifferent doctors prescribing high doses to unknowing patients through the 1950s and 1960s.[citation needed] In the late 1950s and 1960s, increasing published reports of barbiturate overdoses and dependence problems led physicians to cut back their prescription, particularly for spurious requests. This eventually led to the scheduling of barbiturates as controlled drugs. In the Netherlands, the Opium Law classifies all barbiturates as List II drugs, with the exception of secobarbital, which is List I. There is a small group of List II drugs for which doctors have to write the prescriptions according to the same, tougher guidelines as those for List I drugs (writing the prescription in full in letters, listing the patients name, and have to contain the name and initials, address, city and telephone number of the licensed prescriber issuing the prescriptions, as well as the name and initials, address and city of the person the prescription is issued to). Among that group of drugs are the barbiturates amobarbital, butalbital, cyclobarbital, and pentobarbital. In the United States, the Controlled Substances Act
Controlled Substances Act
of 1970 classified most barbiturates as controlled substances—and they remain so as of September 2015[update]. Barbital, methylphenobarbital (also known as mephobarbital), and phenobarbital are designated schedule IV drugs, and "Any substance which contains any quantity of a derivative of barbituric acid, or any salt of a derivative of barbituric acid"[26] (all other barbiturates) were designated as schedule III. Under the original CSA, no barbiturates were placed in schedule I, II, or V,[27] however amobarbital, pentobarbital, and secobarbital are schedule II controlled substances unless they are in a suppository dosage form.[28] In 1971, the Convention on Psychotropic Substances
Convention on Psychotropic Substances
was signed in Vienna. Designed to regulate amphetamines, barbiturates, and other synthetics, the 34th version of the treaty, as of 25 January 2014[update], regulates secobarbital as schedule II, amobarbital, butalbital, cyclobarbital, and pentobarbital as schedule III, and allobarbital, barbital, butobarbital, mephobarbital, phenobarbital, butabarbital, and vinylbital as schedule IV on its "Green List".[29] The combination medication Fioricet, consisting of butalbital, caffeine, and paracetamol (acetaminophen), however, is specifically exempted from controlled substance status, while its sibling Fiorinal, which contains aspirin instead of paracetamol and may contain codeine phosphate, remains a schedule III drug. Recreational use[edit] Recreational users report that a barbiturate high gives them feelings of relaxed contentment and euphoria. Physical and psychological dependence may also develop with repeated use.[30] Chronic misuse of barbiturates is associated with significant morbidity. One study found that 11% of males and 23% of females with a sedative-hypnotic misuse die by suicide.[31] Other effects of barbiturate intoxication include drowsiness, lateral and vertical nystagmus, slurred speech and ataxia, decreased anxiety and loss of inhibitions. Barbiturates
Barbiturates
are also used to alleviate the adverse or withdrawal effects of illicit drug use, in a manner similar to long-acting benzodiazepines such as diazepam and clonazepam.[32][33] Drug users tend to prefer short-acting and intermediate-acting barbiturates.[34] The most commonly used are amobarbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal). A combination of amobarbital and secobarbital (called Tuinal) is also highly used. 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. Slang terms for barbiturates include barbs, bluebirds, dolls, wallbangers, yellows, downers, goofballs, sleepers, 'reds & blues' and tooties.[35] Other uses in chemistry[edit] In 1988, the synthesis and binding studies of an artificial receptor binding barbiturates by 6 complementary hydrogen bonds was published.[36] 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. Sodium barbital and barbital have also been used as pH buffers for biological research, e.g., in immunoelectrophoresis or in fixative solutions.[37][38] Examples[edit]

Generic structure of a barbiturate, including numbering scheme

Barbiturates

Short Name R1 R2 IUPAC Name

allobarbital CH2CHCH2 CH2CHCH2 5,5-diallylbarbiturate

amobarbital[39] CH2CH3 (CH2)2CH(CH3)2 5-ethyl-5-isopentyl-barbiturate

aprobarbital CH2CHCH2 CH(CH3)2 5-allyl-5-isopropyl-barbiturate

alphenal CH2CHCH2 C6H5 5-allyl-5-phenyl-barbiturate

barbital CH2CH3 CH2CH3 5,5-diethylbarbiturate

brallobarbital CH2CHCH2 CH2CBrCH2 5-allyl-5-(2-bromo-allyl)-barbiturate

pentobarbital[39] CH2CH3 CHCH3(CH2)2CH3 5-ethyl-5-(1-methylbutyl)-barbiturate

phenobarbital[39] CH2CH3 C6H5 5-ethyl-5-phenylbarbiturate

secobarbital[39] CH2CHCH2 CHCH3(CH2)2CH3 5-[(2R)-pentan-2-yl]-5-prop-2-enyl-barbiturate; 5-allyl-5-[(2R)-pentan-2-yl]-barbiturate

Thiopental
Thiopental
is a barbiturate with one of the C-O double bonds (with the carbon being labelled 2 in the diagram to the right) replaced with a C-S double bond, R1 being CH2CH3 and R2 being CH(CH3)CH2CH2CH3. See also[edit]

Pharmacy and Pharmacology portal

Benzodiazepines Psycholeptic The Dille–Koppanyi reagent, used as a spot test for barbiturates. The Zwikker reagent, also used as a spot test for barbiturates.

References[edit]

^ The most often cited standard pronunciation is /ˌbɑːrˈbɪtʃərɪt/; however, at least in the U.S., the more commonly used colloquial pronunciation is /ˌbɑːrˈbɪtʃuːɪt/, with no "r" sound.

^ Vaux, Bert and Scott Golder. 2003. The Harvard Dialect Survey. Cambridge, MA: Harvard University Linguistics Department. ^ "DIGNITAS". Archived from the original on 21 July 2011. Retrieved 2011-06-14.  ^ Edward R. Garrett; Jacek T. Bojarski†; Gerald J. Yakatan (21 Sep 2006). "Kinetics of hydrolysis of barbituric acid derivatives". Journal of Pharmaceutical Sciences. 60 (8): 1145–54. doi:10.1002/jps.2600600807. PMID 5127086.  ^ Whitlock FA (June 14, 1975). "Suicide in Brisbane, 1956 to 1973: the drug-death epidemic". Med J Aust. 1 (24): 737–43. PMID 239307.  ^ Johns MW (1975). "Sleep and hypnotic drugs". Drugs. 9 (6): 448–78. doi:10.2165/00003495-197509060-00004. PMID 238826.  ^ Jufe, GS (2007). "Nuevos hipnóticos: perspectivas desde la fisiología del sueño [New hypnotics: perspectives from sleep physiology]" (PDF). Vertex (Buenos Aires, Argentina) (in Spanish). 18 (74): 294–9. PMID 18265473.  ^ "Administration and Compounding Of Euthanasic Agents". Archived from the original on 7 June 2008. Retrieved 15 July 2008.  ^ Daniel Engber. "Why do lethal injections have three drugs?". Slate Magazine. Archived from the original on 25 July 2008. Retrieved 15 July 2008.  ^ "Neuroscience for Kids - Barbiturates". Archived from the original on 16 June 2008. Retrieved 2008-06-02.  ^ Stocks, JT (1998). "Recovered memory therapy: a dubious practice technique". Social work. 43 (5): 423–36. doi:10.1093/sw/43.5.423. PMID 9739631.  ^ Nutt, D; King, LA; Saulsbury, W; Blakemore, C (24 March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". Lancet. 369 (9566): 1047–53. doi:10.1016/s0140-6736(07)60464-4. PMID 17382831.  ^ WebMD. "Toxicity, Barbiturate". eMedicine. Archived from the original on 20 July 2008. Retrieved 15 July 2008.  ^ Nau H; Kuhnz W; Egger HJ; Rating D; Helge H (Nov 1982). " Anticonvulsants
Anticonvulsants
during pregnancy and lactation. Transplacental, maternal and neonatal pharmacokinetics". Clin Pharmacokinet. 7 (6): 508–43. doi:10.2165/00003088-198207060-00003. PMID 6819105.  ^ "Livertox".  ^ Löscher, W.; Rogawski, M. A. (2012). "How theories evolved concerning the mechanism of action of barbiturates". Epilepsia. 53: 12–25. doi:10.1111/epi.12025. PMID 23205959.  ^ Chiara, D. C.; Jayakar, S. S.; Zhou, X.; Zhang, X.; Savechenkov, P. Y.; Bruzik, K. S.; Miller, K. W.; Cohen, J. B. (15 May 2013). "Specificity of Intersubunit General Anesthetic-binding Sites in the Transmembrane Domain of the Human α1β3γ2 γ-Aminobutyric Acid
Acid
Type A (GABAA) Receptor". Journal of Biological Chemistry. 288 (27): 19343–19357. doi:10.1074/jbc.M113.479725. PMC 3707639 . PMID 23677991.  ^ 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 0-07-142280-3.  ^ Neil Harrison; Wallace B Mendelson; Harriet de Wit (2000). "Barbiturates". Neuropsychopharmacology. Retrieved 15 July 2008. ... Barbiturates
Barbiturates
therefore promote entry of GABA-activated channels into a long-lived open state, whereas [benzodiazepines] increase only the frequency of channel opening into the initial open state. These mechanistic studies reveal interesting details of the changes in channel gating caused by barbiturates but as yet have yielded no insights into the molecular sites of action. An additional interesting effect of barbiturates is direct gating of the channels, i.e., the barbiturates may open the channel even in the absence of GABA. This usually occurs at significantly higher concentrations than those that potentiate the actions of GABA; these concentrations also are generally higher than those required for clinically effective anesthesia.  ^ Siegel, George J.; Bernard W. Agranoff; Stephen K. Fisher; R. Wayne Albers; Michael D. Uhler (1999) [1998]. "Part 2 Chapter 16". Basic Neurochemistry - Molecular, Cellular and Medical Aspects (Sixth ed.). Lippincott Williams and Wilkins. ISBN 0-397-51820-X. Retrieved July 2008.  Check date values in: access-date= (help) ^ Weber, M; Motin, L; Gaul, S; Beker, F; Fink, RH; Adams, DJ (January 2005). "Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+
Ca2+
transients in rat intracardiac ganglion neurons". British Journal of Pharmacology. 144 (1): 98–107. doi:10.1038/sj.bjp.0705942. PMC 1575970 . PMID 15644873.  ^ 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.  ^ a b "Barbiturates". Archived from the original on 7 November 2007. Retrieved 2007-10-31.  ^ Medical Curiosities. Youngson, Robert M. London: Robinson Publishing, 1997. Page 276. ^ 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 978-1-58562-276-4.  ^ Sneader, Walter (2005-06-23). Drug Discovery. John Wiley and Sons. p. 369. ISBN 0-471-89979-8.  ^ Pub. L. 91-513, October 27, 1970, Sec. 202(c) Sched. III(b)(1) ^ 21 U.S.C. § 812 ^ 21 U.S.C. § §1308.12 ^ "List of Psychotropic Substances under International Control ("Green List")" (PDF). International Narcotics Control Board. 25 January 2014. Retrieved 19 December 2013.  ^ Schlatter J; Sitbon N; Saulnier JL (February 17, 2001). "[Drugs and drug abusers]". Presse Med. 30 (6): 282–7. PMID 11252979.  ^ Allgulander C, Ljungberg L, Fisher LD (May 1987). "Long-term prognosis in addiction on sedative and hypnotic drugs analyzed with the Cox regression model". Acta Psychiatr Scand. 75 (5): 521–31. doi:10.1111/j.1600-0447.1987.tb02828.x. PMID 3604738.  ^ Emedicine Health. " Barbiturate
Barbiturate
Abuse". p. 1. Archived from the original on 2 August 2008. Retrieved 15 July 2008.  ^ 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.  ^ Coupey SM (August 1997). "Barbiturates". Pediatr Rev. 18 (8): 260–4. doi:10.1542/pir.18-8-260. PMID 9255991.  ^ 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.  ^ Chang, Suk Kyu.; Hamilton, Andrew D. (1988). "Molecular recognition of biologically interesting substrates: Synthesis of an artificial receptor for barbiturates employing six hydrogen bonds". Journal of the American Chemical Society. 110 (4): 1318–1319. doi:10.1021/ja00212a065.  ^ "Wolf D. Kuhlmann, "Buffer Solutions"" (PDF). 10 September 2006. Retrieved 28 July 2014.  ^ Steven E. Ruzin (1999). Plant Microtechnique and Microscopy. Oxford University Press. Retrieved 28 July 2014.  ^ a b c d Smith, Roger; Bogusz, Maciej J (September 22, 2011). Forensic Science (2 ed.). Elsevier. p. 245. ISBN 9780080554259. Retrieved 21 December 2013. 

External links[edit]

Look up barbiturate in Wiktionary, the free dictionary.

U.S. Drug Enforcement Administration Source for some public domain text used on this page. History of Barbiturates National Institute on Drug Abuse: "NIDA for Teens: Prescription Depressant
Depressant
Medications".

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Barbiturates: Barbexaclone Metharbital Methylphenobarbital Pentobarbital Phenobarbital# Primidone; Carbamates: Felbamate; Benzodiazepines: Clobazam Clonazepam Clorazepate Diazepam# Lorazepam# Midazolam Nimetazepam Nitrazepam Temazepam; Others: Bromide (potassium bromide, sodium bromide) Imepitoin Paraldehyde Stiripentol

GABA-T inhibitors

Fatty acids (and related): Valproate Valpromide Valproate
Valproate
pivoxil Vigabatrin

Others

GABAR agonists: Progabide; GAT-1 inhibitors: Tiagabine

Channel modulators

Sodium blockers

Hydantoins: Ethotoin Fosphenytoin Mephenytoin Phenytoin#; Ureides: Acetylpheneturide Chlorphenacemide Phenacemide‡ Pheneturide; Fatty acids: Valproate Valpromide Valproate
Valproate
pivoxil; Carboxamides: Carbamazepine# Eslicarbazepine acetate Oxcarbazepine; Others: Lacosamide Lamotrigine# Rufinamide Topiramate Zonisamide

Calcium blockers

Oxazolidinediones: Ethadione Paramethadione Trimethadione; Succinimides: Ethosuximide# Mesuximide Phensuximide; Gabapentinoids: Gabapentin Pregabalin; Others: Imepitoin Lamotrigine# Topiramate Zonisamide

Potassium openers

Retigabine

Others

CA inhibitors

Sulfonamides: Acetazolamide Ethoxzolamide Sultiame Topiramate Zonisamide

Others

Albutoin Beclamide Brivaracetam Etiracetam Levetiracetam Perampanel

#WHO-EM ‡Withdrawn from market Clinical trials:

†Phase III §Never to phase III

v t e

Anxiolytics (N05B)

5-HT1AR agonists

Buspirone Gepirone† Tandospirone

GABAAR PAMs

Benzodiazepines: Adinazolam Alprazolam Bromazepam Camazepam Chlordiazepoxide Clobazam Clonazepam Clorazepate Clotiazepam Cloxazolam Diazepam# Ethyl loflazepate Etizolam Fludiazepam Halazepam Ketazolam Lorazepam# Medazepam Nordazepam Oxazepam Pinazepam Prazepam; Others: Alpidem‡ Barbiturates
Barbiturates
(e.g., phenobarbital) Carbamates (e.g., meprobamate) Chlormezanone‡ Ethanol
Ethanol
(alcohol) Etifoxine Imepitoin; Herbs: Kava Skullcap Valerian

Gabapentinoids (α2δ VDCC blockers)

Gabapentin Gabapentin
Gabapentin
enacarbil Phenibut Pregabalin

Antidepressants

SSRIs (e.g., escitalopram) SNRIs (e.g., duloxetine) SARIs (e.g., trazodone) TCAs (e.g., clomipramine) TeCAs (e.g., mirtazapine) MAOIs (e.g., phenelzine); Others: Agomelatine Bupropion Tianeptine Vilazodone Vortioxetine

Sympatholytics (Antiadrenergics)

Alpha-1 blockers (e.g., prazosin) Alpha-2 agonists (e.g., clonidine, dexmedetomidine, guanfacine) Beta blockers (e.g., propranolol)

Others

Benzoctamine Cannabidiol Cycloserine Fabomotizole Hydroxyzine Kanna Lavender Lorpiprazole Mebicar Mepiprazole Nicotine Opipramol Oxaflozane‡ Phenaglycodol Phenibut Picamilon Selank Tiagabine Tofisopam Validolum

#WHO-EM ‡Withdrawn from market Clinical trials:

†Phase III §Never to phase III

v t e

Hypnotics/sedatives (N05C)

GABAA

Alcohols

2M2B Chloralodol Ethanol
Ethanol
(alcohol) Ethchlorvynol Methylpentynol Trichloroethanol

Barbiturates

Allobarbital Amobarbital Aprobarbital Barbital Butabarbital Butobarbital Cyclobarbital Ethallobarbital Heptabarb Hexobarbital Mephobarbital Methohexital Narcobarbital Pentobarbital Phenallymal Phenobarbital Propylbarbital Proxibarbal Reposal Secobarbital Talbutal Thiamylal Thiopental Thiotetrabarbital Vinbarbital Vinylbital

Benzodiazepines

Brotizolam Cinolazepam Climazolam Doxefazepam Estazolam Flunitrazepam Flurazepam Flutoprazepam Lorazepam Loprazolam Lormetazepam Midazolam Nimetazepam Nitrazepam Phenazepam Quazepam Temazepam Triazolam

Carbamates

Carisoprodol Emylcamate Ethinamate Hexapropymate Meprobamate Methocarbamol Phenprobamate Procymate Tybamate

Imidazoles

Etomidate Metomidate Propoxate

Monoureides

Acecarbromal Apronal
Apronal
(apronalide) Bromisoval Capuride Carbromal Ectylurea

Neuroactive steroids

Acebrochol Allopregnanolone Alphadolone Alphaxolone Eltanolone Hydroxydione Minaxolone Progesterone

Nonbenzodiazepines

Eszopiclone Indiplon Lirequinil Necopidem Pazinaclone Saripidem Suproclone Suriclone Zaleplon Zolpidem Zopiclone

Phenols

Propofol

Piperidinediones

Glutethimide Methyprylon Pyrithyldione Piperidione

Quinazolinones

Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone

Others

Acetophenone Acetylglycinamide chloral hydrate Bromide compounds

Lithium bromide Potassium bromide Sodium bromide

Centalun Chloral
Chloral
betaine Chloral
Chloral
hydrate Chloralose Clomethiazole Dichloralphenazone Gaboxadol Kavalactones Loreclezole Paraldehyde Petrichloral Sulfonylalkanes

Sulfonmethane
Sulfonmethane
(sulfonal) Tetronal Trional

Triclofos Sesquiterpene

Isovaleramide Isovaleric acid Valerenic acid

GABAB

1,4-Butanediol 4-Fluorophenibut Aceburic acid Baclofen GABOB GHB (sodium oxybate) GBL GVL Phenibut Tolibut

H1

Antihistamines

Captodiame Cyproheptadine Diphenhydramine Doxylamine Hydroxyzine Methapyrilene Perlapine Pheniramine Promethazine Propiomazine

Antidepressants

Serotonin antagonists and reuptake inhibitors

Etoperidone Nefazodone Trazodone

Tricyclic antidepressants

Amitriptyline Doxepin Trimipramine, etc.

Tetracyclic antidepressants

Mianserin Mirtazapine, etc.

Antipsychotics

Typical antipsychotics

Chlorpromazine Thioridazine, etc.

Atypical antipsychotics

Olanzapine Quetiapine Risperidone, etc.

α2-Adrenergic

Clonidine Detomidine Dexmedetomidine Lofexidine Medetomidine Romifidine Tizanidine Xylazine

5-HT2A

Antidepressants

Trazodone Tricyclic antidepressants

Amitriptyline Doxepin Trimipramine, etc.

Tetracyclic antidepressants

Mianserin Mirtazapine, etc.

Antipsychotics

Typical antipsychotics

Chlorpromazine Thioridazine, etc.

Atypical antipsychotics

Olanzapine Quetiapine Risperidone, etc.

Others

Niaprazine

Melatonin

Agomelatine Melatonin Ramelteon Tasimelteon

Orexin

Almorexant Filorexant Suvorexant

α2δ VDCC

Gabapentin Gabapentin
Gabapentin
enacarbil Mirogabalin Phenibut Pregabalin

Others

Cannabidiol

Cannabis

Chlorophenylalkyldiols

Fenpentadiol Metaglycodol Phenaglycodol

Diethylpropanediol Evoxine Fenadiazole Guaifenesin-related muscle relaxants

Chlorphenesin Mephenesin Mephenoxalone Metaxalone Methocarbamol

Opioids (e.g., morphine) Passion flower Scopolamine Trazodone UMB68 Valnoctamide

v t e

Insomnia
Insomnia
pharmacotherapies

GABAAR PAMs

Benzodiazepines: Brotizolam Cinolazepam Climazolam Clorazepate Doxefazepam Estazolam Etizolam Flunitrazepam Flurazepam Flutoprazepam Haloxazolam Loprazolam Lormetazepam Midazolam Nimetazepam Nitrazepam Quazepam Temazepam Triazolam; Nonbenzodiazepines/Z-drugs: Eszopiclone Zaleplon Zolpidem Zopiclone; Others: Alcohols (e.g., ethchlorvynol, amylene hydrate, ethanol) Barbiturates
Barbiturates
(e.g., amobarbital, pentobarbital, phenobarbital, secobarbital) Bromides (e.g., potassium bromide, sodium bromide) Carbamates (e.g., meprobamate) Chloral
Chloral
hydrate Clomethiazole Kava Paraldehyde Piperidinediones (e.g., glutethimide) Quinazolinones (e.g., methaqualone) Sulfonmethane Valerian

Antihistamines (H1R inverse agonists)

Alimemazine Captodiame Dimenhydrinate Diphenhydramine Doxylamine Etodroxizine Hydroxyzine Meclizine Methapyrilene Pheniramine Phenyltoloxamine Pimethixene Promethazine Propiomazine Pyrilamine TCAs (e.g., amitriptyline, doxepin, trimipramine) TeCAs (e.g., mirtazapine) Triprolidine

OXR antagonists

Almorexant§ Filorexant§ Lemborexant§ Suvorexant

MTR agonists

Agomelatine Melatonin Ramelteon Tasimelteon

Miscellaneous

Antipsychotics (e.g., quetiapine, olanzapine, chlorpromazine) Ashwagandha Benzoctamine Cannabinoids (e.g., cannabis, dronabinol (THC), nabilone) Chamomile Fenadiazole Gabapentinoids (e.g., gabapentin, pregabalin, phenibut) Hops Lavender Menthyl isovalerate Niaprazine Opioids (e.g., hydrocodone, oxycodone, morphine) Passion flower Scopolamine Serotonin precursors (tryptophan, 5-HTP) Sodium oxybate
Sodium oxybate
(GHB) Sympatholytics (e.g., clonidine, guanfacine) TCAs (e.g., amitriptyline, doxepin, trimipramine) TeCAs (e.g., mirtazapine) Theanine Trazodone Valnoctamide

Pharmacodynamics

v t e

GABAA
GABAA
receptor positive modulators

Alcohols

Brometone Butanol Chloralodol Chlorobutanol
Chlorobutanol
(cloretone) Ethanol
Ethanol
(alcohol) (alcoholic drink) Ethchlorvynol Isobutanol Isopropanol Menthol Methanol Methylpentynol Pentanol Petrichloral Propanol tert-Butanol (2M2P) tert-Pentanol (2M2B) Tribromoethanol Trichloroethanol Triclofos Trifluoroethanol

Barbiturates

(-)-DMBB Allobarbital Alphenal Amobarbital Aprobarbital Barbexaclone Barbital Benzobarbital Benzylbutylbarbiturate Brallobarbital Brophebarbital Butabarbital/Secbutabarbital Butalbital Buthalital Butobarbital Butallylonal Carbubarb Crotylbarbital Cyclobarbital Cyclopentobarbital Difebarbamate Enallylpropymal Ethallobarbital Eterobarb Febarbamate Heptabarb Heptobarbital Hexethal Hexobarbital Metharbital Methitural Methohexital Methylphenobarbital Narcobarbital Nealbarbital Pentobarbital Phenallymal Phenobarbital Phetharbital Primidone Probarbital Propallylonal Propylbarbital Proxibarbital Reposal Secobarbital Sigmodal Spirobarbital Talbutal Tetrabamate Tetrabarbital Thialbarbital Thiamylal Thiobarbital Thiobutabarbital Thiopental Thiotetrabarbital Valofane Vinbarbital Vinylbital

Benzodiazepines

2-Oxoquazepam 3-Hydroxyphenazepam Adinazolam Alprazolam Arfendazam Avizafone Bentazepam Bretazenil Bromazepam Brotizolam Camazepam Carburazepam Chlordiazepoxide Ciclotizolam Cinazepam Cinolazepam Clazolam Climazolam Clobazam Clonazepam Clonazolam Cloniprazepam Clorazepate Clotiazepam Cloxazolam CP-1414S Cyprazepam Delorazepam Demoxepam Diazepam Diclazepam Doxefazepam Elfazepam Estazolam Ethyl carfluzepate Ethyl dirazepate Ethyl loflazepate Etizolam EVT-201 FG-8205 Fletazepam Flubromazepam Flubromazolam Fludiazepam Flunitrazepam Flunitrazolam Flurazepam Flutazolam Flutemazepam Flutoprazepam Fosazepam Gidazepam Halazepam Haloxazolam Iclazepam Imidazenil Irazepine Ketazolam Lofendazam Lopirazepam Loprazolam Lorazepam Lormetazepam Meclonazepam Medazepam Menitrazepam Metaclazepam Mexazolam Midazolam Motrazepam N-Desalkylflurazepam Nifoxipam Nimetazepam Nitrazepam Nitrazepate Nitrazolam Nordazepam Nortetrazepam Oxazepam Oxazolam Phenazepam Pinazepam Pivoxazepam Prazepam Premazepam Proflazepam Pyrazolam QH-II-66 Quazepam Reclazepam Remimazolam Rilmazafone Ripazepam Ro48-6791 Ro48-8684 SH-053-R-CH3-2′F Sulazepam Temazepam Tetrazepam Tolufazepam Triazolam Triflubazam Triflunordazepam
Triflunordazepam
(Ro5-2904) Tuclazepam Uldazepam Zapizolam Zolazepam Zomebazam

Carbamates

Carisbamate Carisoprodol Clocental Cyclarbamate Difebarbamate Emylcamate Ethinamate Febarbamate Felbamate Hexapropymate Lorbamate Mebutamate Meprobamate Nisobamate Pentabamate Phenprobamate Procymate Styramate Tetrabamate Tybamate

Flavonoids

6-Methylapigenin Ampelopsin
Ampelopsin
(dihydromyricetin) Apigenin Baicalein Baicalin Catechin EGC EGCG Hispidulin Linarin Luteolin Rc-OMe Skullcap constituents (e.g., baicalin) Wogonin

Imidazoles

Etomidate Metomidate Propoxate

Kava
Kava
constituents

10-Methoxyyangonin 11-Methoxyyangonin 11-Hydroxyyangonin Desmethoxyyangonin 11-Methoxy-12-hydroxydehydrokavain 7,8-Dihydroyangonin Kavain 5-Hydroxykavain 5,6-Dihydroyangonin 7,8-Dihydrokavain 5,6,7,8-Tetrahydroyangonin 5,6-Dehydromethysticin Methysticin 7,8-Dihydromethysticin Yangonin

Monoureides

Acecarbromal Apronal
Apronal
(apronalide) Bromisoval Carbromal Capuride Ectylurea

Neuroactive steroids

Acebrochol Allopregnanolone
Allopregnanolone
(brexanolone) Alfadolone Alfaxalone 3α-Androstanediol Androstenol Androsterone Certain anabolic-androgenic steroids Cholesterol DHDOC 3α-DHP 5α-DHP 5β-DHP DHT Etiocholanolone Ganaxolone Hydroxydione Minaxolone ORG-20599 ORG-21465 P1-185 Pregnanolone
Pregnanolone
(eltanolone) Progesterone Renanolone SAGE-105 SAGE-217 SAGE-324 SAGE-516 SAGE-689 SAGE-872 Testosterone THDOC

Nonbenzodiazepines

β-Carbolines: Abecarnil Gedocarnil Harmane SL-651,498 ZK-93423

Cyclopyrrolones: Eszopiclone Pagoclone Pazinaclone Suproclone Suriclone Zopiclone

Imidazopyridines: Alpidem DS-1 Necopidem Saripidem Zolpidem

Pyrazolopyrimidines: Divaplon Fasiplon Indiplon Lorediplon Ocinaplon Panadiplon Taniplon Zaleplon

Others: Adipiplon CGS-8216 CGS-9896 CGS-13767 CGS-20625 CL-218,872 CP-615,003 CTP-354 ELB-139 GBLD-345 Imepitoin JM-1232 L-838,417 Lirequinil
Lirequinil
(Ro41-3696) NS-2664 NS-2710 NS-11394 Pipequaline ROD-188 RWJ-51204 SB-205,384 SX-3228 TGSC01AA TP-003 TPA-023 TP-13 U-89843A U-90042 Viqualine Y-23684

Phenols

Fospropofol Propofol Thymol

Piperidinediones

Glutethimide Methyprylon Piperidione Pyrithyldione

Pyrazolopyridines

Cartazolate Etazolate ICI-190,622 Tracazolate

Quinazolinones

Afloqualone Cloroqualone Diproqualone Etaqualone Mebroqualone Mecloqualone Methaqualone Methylmethaqualone Nitromethaqualone SL-164

Volatiles/gases

Acetone Acetophenone Acetylglycinamide chloral hydrate Aliflurane Benzene Butane Butylene Centalun Chloral Chloral
Chloral
betaine Chloral
Chloral
hydrate Chloroform Cryofluorane Desflurane Dichloralphenazone Dichloromethane Diethyl ether Enflurane Ethyl chloride Ethylene Fluroxene Gasoline Halopropane Halothane Isoflurane Kerosine Methoxyflurane Methoxypropane Nitric oxide Nitrogen Nitrous oxide Norflurane Paraldehyde Propane Propylene Roflurane Sevoflurane Synthane Teflurane Toluene Trichloroethane (methyl chloroform) Trichloroethylene Vinyl ether

Others/unsorted

3-Hydroxybutanal α-EMTBL AA-29504 Avermectins (e.g., ivermectin) Bromide compounds (e.g., lithium bromide, potassium bromide, sodium bromide) Carbamazepine Chloralose Chlormezanone Clomethiazole DEABL Dihydroergolines (e.g., dihydroergocryptine, dihydroergosine, dihydroergotamine, ergoloid (dihydroergotoxine)) DS2 Efavirenz Etazepine Etifoxine Fenamates (e.g., flufenamic acid, mefenamic acid, niflumic acid, tolfenamic acid) Fluoxetine Flupirtine Hopantenic acid Lanthanum Lavender oil Lignans (e.g., 4-O-methylhonokiol, honokiol, magnolol, obovatol) Loreclezole Menthyl isovalerate
Menthyl isovalerate
(validolum) Monastrol Niacin Nicotinamide
Nicotinamide
(niacinamide) Org 25,435 Phenytoin Propanidid Retigabine
Retigabine
(ezogabine) Safranal Seproxetine Stiripentol Sulfonylalkanes (e.g., sulfonmethane (sulfonal), tetronal, trional) Terpenoids (e.g., borneol) Topiramate Valerian constituents (e.g., isovaleric acid, isovaleramide, valerenic acid, valerenol)

Unsorted benzodiazepine site positive modulators: α-Pinene MRK-409 (MK-0343) TCS-1105 TCS-1205

See also: Receptor/signaling modulators • GABA
GABA
receptor modulators • GABA
GABA
metabolism/transport modulators

v t e

Glycine receptor
Glycine receptor
modulators

Receptor (ligands)

GlyR

Agonists: β-Alanine β-ABA (BABA) β-AIBA Caesium D-Alanine D-Serine GABA Glycine Hypotaurine Ivermectin L-Alanine L-Proline L-Serine L-Threonine MDL-27531 Milacemide Picolinic acid Propofol Quisqualamine Sarcosine Taurine

Positive modulators: Alcohols (e.g., brometone, chlorobutanol (chloretone), ethanol (alcohol), tert-butanol (2M2P), tribromoethanol, trichloroethanol, trifluoroethanol) Alkylbenzene sulfonate Anandamide Barbiturates
Barbiturates
(e.g., pentobarbital, sodium thiopental) Chlormethiazole D12-116 Dihydropyridines (e.g., nicardipine) Etomidate Ginseng
Ginseng
constituents (e.g., ginsenosides (e.g., ginsenoside-Rf)) Glutamic acid
Glutamic acid
(glutamate) Ivermectin Ketamine Neuroactive steroids (e.g., alfaxolone, pregnenolone (eltanolone), pregnenolone acetate, minaxolone, ORG-20599) Nitrous oxide Penicillin G Propofol Tamoxifen Tetrahydrocannabinol Triclofos Tropeines (e.g., atropine, bemesetron, cocaine, LY-278584, tropisetron, zatosetron) Volatiles/gases (e.g., chloral hydrate, chloroform, desflurane, diethyl ether (ether), enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, toluene, trichloroethane (methyl chloroform), trichloroethylene) Xenon Zinc

Antagonists: 2-Aminostrychnine 2-Nitrostrychnine 4-Phenyl-4-formyl-N-methylpiperidine αEMBTL Bicuculline Brucine Cacotheline Caffeine Colchicine Colubrine Cyanotriphenylborate Dendrobine Diaboline Endocannabinoids (e.g., 2-AG, anandamide (AEA)) Gaboxadol
Gaboxadol
(THIP) Gelsemine iso-THAZ Isobutyric acid Isonipecotic acid Isostrychnine Laudanosine N-Methylbicuculline N-Methylstrychnine N,N-Dimethylmuscimol Nipecotic acid Pitrazepin Pseudostrychnine Quinolines (e.g., 4-hydroxyquinoline, 4-hydroxyquinoline-3-carboxylic acid, 5,7-CIQA, 7-CIQ, 7-TFQ, 7-TFQA) RU-5135 Sinomenine Strychnine Thiocolchicoside Tutin

Negative modulators: Amiloride Benzodiazepines
Benzodiazepines
(e.g., bromazepam, clonazepam, diazepam, flunitrazepam, flurazepam) Corymine Cyanotriphenylborate Daidzein Dihydropyridines (e.g., nicardipine, nifedipine, nitrendipine) Furosemide Genistein Ginkgo constituents (e.g., bilobalide, ginkgolides (e.g., ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide M)) Imipramine NBQX Neuroactive steroids (e.g., 3α-androsterone sulfate, 3β-androsterone sulfate, deoxycorticosterone, DHEA sulfate, pregnenolone sulfate, progesterone) Opioids (e.g., codeine, dextromethorphan, dextrorphan, levomethadone, levorphanol, morphine, oripavine, pethidine, thebaine) Picrotoxin
Picrotoxin
(i.e., picrotin and picrotoxinin) PMBA Riluzole Tropeines (e.g., bemesetron, LY-278584, tropisetron, zatosetron) Verapamil Zinc

NMDAR

See here instead.

Transporter (blockers)

GlyT1

ACPPB ALX-1393 ALX-5407 (NFPS) AMG-747 ASP2535 Bitopertin
Bitopertin
(RG1678/RO4917838) CP-802079 Ethanol
Ethanol
(alcohol) Glycyldodecylamide GSK1018921 LY-2365109 ORG-24598 ORG-25935
ORG-25935
(SCH-900435) PF-02545920 PF-03463275 PF-04958242 Sarcosine SSR-103,800 SSR-504,734

GlyT2

Amoxapine Ethanol
Ethanol
(alcohol) NAGly Opiranserin (VVZ-149) ORG-25543 VVZ-368

See also Receptor/signaling modulators GABA
GABA
receptor modulators GABAA
GABAA
receptor positive modulators Ionotropic glutamate receptor
Ionotropic glutamate receptor
modulators

v t e

Ion channel modulators

Calcium

VDCCs

Blockers

L-type-selective: Dihydropyridines: Amlodipine Aranidipine Azelnidipine Barnidipine Clevidipine Cronidipine Darodipine Dexniguldipine Elgodipine Elnadipine Felodipine Flordipine Furnidipine Iganidipine Isradipine Lacidipine Lemildipine Lercanidipine Levamlodipine Levniguldipine Manidipine Mepirodipine Mesudipine Nicardipine Nifedipine Niguldipine Niludipine Nilvadipine Nimodipine Nisoldipine Nitrendipine Olradipine Oxodipine Palonidipine Pranidipine Ryodipine (riodipine) Sagandipine Sornidipine Teludipine Tiamdipine Trombodipine Vatanidipine; Diltiazem
Diltiazem
derivatives: Clentiazem Diltiazem Iprotiazem Nictiazem Siratiazem; Phenylalkylamines: Anipamil Dagapamil Devapamil Dexverapamil Emopamil Etripamil Falipamil Gallopamil Levemopamil Nexopamil Norverapamil Ronipamil Tiapamil Verapamil; Others: AH-1058 Brinazarone Budiodarone Celivarone Cyproheptadine Dronedarone Fantofarone SR-33805 Tetrahydropalmatine

N-type-selective: ω-Conotoxins ω- Conotoxin
Conotoxin
GVIA Caroverine Huwentoxin XVI Leconotide (ω-conotoxin CVID) PD-173212 Ralfinamide Safinamide Z160 Ziconotide
Ziconotide
(ω-conotoxin MVIIA)

P-type-selective: ω-Agatoxin IVA ω-Agatoxin IVB

R-type-selective: SNX-482

T-type-selective: ABT-639 ML-218 Niflumic acid NNC 55-0396 ProTx I Z944 Zonisamide

Non-selective: ω-Agatoxin TK ω- Conotoxin
Conotoxin
MVIIC Benidipine Bepridil Cilnidipine Cinnarizine Dotarizine Efonidipine Flunarizine Lamotrigine Levetiracetam Lomerizine Loperamide Mibefradil NP078585 Ruthenium red TROX-1

α2δ subunit-selective (gabapentinoids): 4-Methylpregabalin Arbaclofen Arbaclofen
Arbaclofen
placarbil Atagabalin Baclofen Gabapentin Gabapentin
Gabapentin
enacarbil Imagabalin Mirogabalin PD-200,347 PD-217,014 PD-299,685 Phenibut Pregabalin

Others/unsorted: Bencyclane Berbamine Bevantolol Canadine Carboxyamidotriazole Cycleanine Dauricine Dimeditiapramine Diproteverine Enpiperate Eperisone Elpetrigine Ethadione Ethanol
Ethanol
(alcohol) Ethosuximide Fasudil Fendiline Fostedil Imepitoin JTV-519 Lidoflazine Magnesium Manoalide Mesuximide Monatepil Naftopidil Ochratoxin A Osthol Otilonium bromide Paramethadione Phensuximide Pinaverium bromide Prenylamine Rhynchophylline Sesamodil Silperisone Sipatrigine Terodiline Tetrandrine Tolperisone Trimethadione Valperinol

Activators

L-type-selective: Bay K8644

Potassium

VGKCs

Blockers

3,4-Diaminopyridine
3,4-Diaminopyridine
(amifampridine) 4-Aminopyridine
4-Aminopyridine
(fampridine/dalfampridine) Adekalant Almokalant Amiodarone Azimilide Bretylium Bunaftine Charybdotoxin Clamikalant Conotoxins Dalazatide Dendrotoxin Dofetilide Dronedarone E-4031 Hanatoxin HgeTx1 HsTx1 Ibutilide Inakalant Kaliotoxin Linopirdine Lolitrem B Maurotoxin Nifekalant Notoxin Paxilline Pinokalant Quinidine ShK-186 Sotalol Tedisamil Terikalant Tetraethylammonium Vernakalant

hERG (KCNH2, Kv11.1)-specific: Ajmaline Amiodarone AmmTX3 Astemizole Azaspiracid AZD1305 Azimilide Bedaquiline BeKm-1 BmTx3 BRL-32872 Chlorpromazine Cisapride Clarithromycin Darifenacin Dextropropoxyphene Diallyl trisulfide Domperidone E-4031 Ergtoxins Erythromycin Gigactonine Haloperidol Ketoconazole Norpropoxyphene Orphenadrine Pimozide PNU-282,987 Promethazine Quinidine Ranolazine Roxithromycin Sertindole Solifenacin Tamulotoxin Terodiline Terfenadine Thioridazine Tolterodine Vanoxerine Vernakalant

KCNQ (Kv7)-specific: Linopirdine XE-991 Spooky toxin (SsTx)

Activators

KCNQ (Kv7)-specific: Flupirtine Retigabine

IRKs

Blockers

KATP-specific: Acetohexamide Carbutamide Chlorpropamide Glibenclamide
Glibenclamide
(glyburide) Glibornuride Glicaramide Gliclazide Glimepiride Glipizide Gliquidone Glisoxepide Glyclopyramide Glycyclamide Metahexamide Mitiglinide Nateglinide Repaglinide Tolazamide Tolbutamide

GIRK-specific: Barium Caramiphen Cloperastine Clozapine Dextromethorphan Ethosuximide Ifenprodil Tertiapin Tipepidine

Activators

KATP-specific: Aprikalim Bimakalim Cromakalim Diazoxide Emakalim Levcromakalim Mazokalim Minoxidil Naminidil Nicorandil Pinacidil Rilmakalim Sarakalim

GIRK-specific: ML-297 (VU0456810)

KCa

Blockers

BKCa-specific: Ethanol
Ethanol
(alcohol) GAL-021

Activators

BKCa-specific: Flufenamic acid Meclofenamic acid Niflumic acid Nimesulide Rottlerin
Rottlerin
(mallotoxin) Tolfenamic acid

K2Ps

Blockers

12-O-Tetradecanoylphorbol-13-acetate Arachidonic acid Fluoxetine Norfluoxetine

Activators

Riluzole

Sodium

VGSCs

Blockers

Antianginals: Ranolazine

Antiarrhythmics (class I): Ajmaline Aprindine Disopyramide Dronedarone Encainide Flecainide Lidocaine Lorajmine Lorcainide Mexiletine Moricizine Pilsicainide Prajmaline Procainamide Propafenone Quinidine Sparteine Tocainide

Anticonvulsants: Acetylpheneturide Carbamazepine Cenobamate Chlorphenacemide Elpetrigine Eslicarbazepine acetate Ethotoin Fosphenytoin Lacosamide Licarbazepine Mephenytoin Oxcarbazepine Oxitriptyline Phenacemide Pheneturide Phenytoin Rufinamide Sipatrigine Topiramate Sodium valproate Valnoctamide Valproate
Valproate
pivoxil Valproate
Valproate
semisodium Valproic acid Valpromide Zonisamide

Local anesthetics: pFBT Amylocaine Articaine Benzocaine Bupivacaine
Bupivacaine
(Levobupivacaine, Ropivacaine) Butacaine Butamben Chloroprocaine Cinchocaine Cocaine Cyclomethycaine Dimethocaine Diphenhydramine Etidocaine Hexylcaine Iontocaine Lidocaine Mepivacaine Meprylcaine Metabutoxycaine Orthocaine Piperocaine Prilocaine Procaine Propoxycaine Proxymetacaine Risocaine Tetracaine Trimecaine

Analgesics: AZD-3161 DSP-2230 Funapide GDC-0276 NKTR-171 PF-04531083 PF-05089771 Ralfinamide Raxatrigine RG7893 (GDC-0287)

Toxins: Conotoxins Neosaxitoxin Saxitoxin Tetrodotoxin

Others: Buprenorphine Evenamide Menthol
Menthol
(mint) Safinamide Tricyclic antidepressants

Activators

Atracotoxins (Robustoxin, Versutoxin) Batrachotoxin Ciguatoxins Poneratoxin

ENaC

Blockers

Amiloride Benzamil Triamterene

Activators

Solnatide

ASICs

Blockers

A-317567 Amiloride Aspirin Ibuprofen PcTX1

Chloride

CaCCs

Blockers

Crofelemer DIDS Ethacrynic acid Flufenamic acid Fluoxetine Furosemide Glibenclamide Mefloquine Mibefradil Niflumic acid

Activators

Carbachol

CFTR

Blockers

Glibenclamide Lonidamine Piretanide

Activators

1,7-Phenanthroline 1,10-Phenanthroline 4,7-Phenanthroline 7,8-Benzoquinoline Ivacaftor Phenanthridine

Unsorted

Blockers

Bumetanide Flufenamic acid Meclofenamic acid Mefenamic acid Mepacrine Niflumic acid Talniflumate Tolfenamic acid Trifluoperazine

Others

TRPs

See here instead.

See also: Receptor/signaling modulators • Transient receptor potential channel modulators

v t e

Ionotropic glutamate receptor
Ionotropic glutamate receptor
modulators

AMPAR

Agonists: Main site agonists: 5-Fluorowillardiine Acromelic acid (acromelate) AMPA BOAA Domoic acid Glutamate Ibotenic acid Proline Quisqualic acid Willardiine; Positive allosteric modulators: Aniracetam Cyclothiazide CX-516 CX-546 CX-614 Farampator
Farampator
(CX-691, ORG-24448) CX-717 CX-1739 CX-1942 Diazoxide Hydrochlorothiazide
Hydrochlorothiazide
(HCTZ) IDRA-21 LY-392098 LY-395153 LY-404187 LY-451646 LY-503430 Mibampator
Mibampator
(LY-451395) Nooglutyl ORG-26576 Oxiracetam PEPA PF-04958242 Piracetam Pramiracetam S-18986 Tulrampator
Tulrampator
(S-47445, CX-1632)

Antagonists: ACEA-1011 ATPO Becampanel Caroverine CNQX Dasolampanel DNQX Fanapanel
Fanapanel
(MPQX) GAMS Kaitocephalin Kynurenic acid Kynurenine Licostinel
Licostinel
(ACEA-1021) NBQX PNQX Selurampanel Tezampanel Theanine Topiramate YM90K Zonampanel; Negative allosteric modulators: Barbiturates
Barbiturates
(e.g., pentobarbital, sodium thiopental) Cyclopropane Enflurane Ethanol
Ethanol
(alcohol) Evans blue GYKI-52466 GYKI-53655 Halothane Irampanel Isoflurane Perampanel Pregnenolone
Pregnenolone
sulfate Sevoflurane Talampanel; Unknown/unsorted antagonists: Minocycline

KAR

Agonists: Main site agonists: 5-Bromowillardiine 5-Iodowillardiine Acromelic acid (acromelate) AMPA ATPA Domoic acid Glutamate Ibotenic acid Kainic acid LY-339434 Proline Quisqualic acid SYM-2081; Positive allosteric modulators: Cyclothiazide Diazoxide Enflurane Halothane Isoflurane

Antagonists: ACEA-1011 CNQX Dasolampanel DNQX GAMS Kaitocephalin Kynurenic acid Licostinel
Licostinel
(ACEA-1021) LY-382884 NBQX NS102 Selurampanel Tezampanel Theanine Topiramate UBP-302; Negative allosteric modulators: Barbiturates
Barbiturates
(e.g., pentobarbital, sodium thiopental) Enflurane Ethanol
Ethanol
(alcohol) Evans blue NS-3763 Pregnenolone
Pregnenolone
sulfate

NMDAR

Agonists: Main site agonists: AMAA Aspartate Glutamate Homocysteic acid
Homocysteic acid
(L-HCA) Homoquinolinic acid Ibotenic acid NMDA Proline Quinolinic acid Tetrazolylglycine Theanine; Glycine
Glycine
site agonists: β-Fluoro-D-alanine ACBD ACC (ACPC) ACPD AK-51 Apimostinel
Apimostinel
(NRX-1074) B6B21 CCG D-Alanine D-Cycloserine D-Serine DHPG Dimethylglycine Glycine HA-966 L-687414 L-Alanine L-Serine Milacemide Neboglamine
Neboglamine
(nebostinel) Rapastinel
Rapastinel
(GLYX-13) Sarcosine; Polyamine site agonists: Neomycin Spermidine Spermine; Other positive allosteric modulators: 24S-Hydroxycholesterol DHEA (prasterone) DHEA sulfate
DHEA sulfate
(prasterone sulfate) Epipregnanolone sulfate Pregnenolone
Pregnenolone
sulfate SAGE-201 SAGE-301 SAGE-718

Antagonists: Competitive antagonists: AP5
AP5
(APV) AP7 CGP-37849 CGP-39551 CGP-39653 CGP-40116 CGS-19755 CPP Kaitocephalin LY-233053 LY-235959 LY-274614 MDL-100453 Midafotel
Midafotel
(d-CPPene) NPC-12626 NPC-17742 PBPD PEAQX Perzinfotel PPDA SDZ-220581 Selfotel; Glycine
Glycine
site antagonists: 4-Cl-KYN (AV-101) 5,7-DCKA 7-CKA ACC ACEA-1011 ACEA-1328 Apimostinel
Apimostinel
(NRX-1074) AV-101 Carisoprodol CGP-39653 CNQX D-Cycloserine DNQX Felbamate Gavestinel GV-196771 Harkoseride Kynurenic acid Kynurenine L-689560 L-701324 Licostinel
Licostinel
(ACEA-1021) LU-73068 MDL-105519 Meprobamate MRZ 2/576 PNQX Rapastinel
Rapastinel
(GLYX-13) ZD-9379; Polyamine site antagonists: Arcaine Co 101676 Diaminopropane Diethylenetriamine Huperzine A Putrescine; Uncompetitive pore blockers (mostly dizocilpine site): 2-MDP 3-HO-PCP 3-MeO-PCE 3-MeO-PCMo 3-MeO-PCP 4-MeO-PCP 8A-PDHQ 18-MC α-Endopsychosin Alaproclate Alazocine
Alazocine
(SKF-10047) Amantadine Aptiganel Argiotoxin-636 Arketamine ARL-12495 ARL-15896-AR ARL-16247 Budipine Coronaridine Delucemine
Delucemine
(NPS-1506) Dexoxadrol Dextrallorphan Dextromethadone Dextromethorphan Dextrorphan Dieticyclidine Diphenidine Dizocilpine Ephenidine Esketamine Etoxadrol Eticyclidine Fluorolintane Gacyclidine Ibogaine Ibogamine Indantadol Ketamine Ketobemidone Lanicemine Levomethadone Levomethorphan Levomilnacipran Levorphanol Loperamide Memantine Methadone Methorphan Methoxetamine Methoxphenidine Milnacipran Morphanol NEFA Neramexane Nitromemantine Noribogaine Norketamine Orphenadrine PCPr PD-137889 Pethidine
Pethidine
(meperidine) Phencyclamine Phencyclidine Propoxyphene Remacemide Rhynchophylline Rimantadine Rolicyclidine Sabeluzole Tabernanthine Tenocyclidine Tiletamine Tramadol; Ifenprodil
Ifenprodil
(NR2B) site antagonists: Besonprodil Buphenine
Buphenine
(nylidrin) CO-101244 (PD-174494) Eliprodil Haloperidol Isoxsuprine Radiprodil (RGH-896) Rislenemdaz
Rislenemdaz
(CERC-301, MK-0657) Ro 8-4304 Ro 25-6981 Safaprodil Traxoprodil
Traxoprodil
(CP-101606); NR2A-selective antagonists: MPX-004 MPX-007 TCN-201 TCN-213; Cations: Hydrogen Magnesium Zinc; Alcohols/volatile anesthetics/related: Benzene Butane Chloroform Cyclopropane Desflurane Diethyl ether Enflurane Ethanol
Ethanol
(alcohol) Halothane Hexanol Isoflurane Methoxyflurane Nitrous oxide Octanol Sevoflurane Toluene Trichloroethane Trichloroethanol Trichloroethylene Urethane Xenon Xylene; Unknown/unsorted antagonists: ARR-15896 Bumetanide Caroverine Conantokin D-αAA Dexanabinol Flufenamic acid Flupirtine FPL-12495 FR-115427 Furosemide Hodgkinsine Ipenoxazone (MLV-6976) MDL-27266 Metaphit Minocycline MPEP Niflumic acid Pentamidine Pentamidine
Pentamidine
isethionate Piretanide Psychotridine Transcrocetin
Transcrocetin
(saffron)

See also: Receptor/signaling modulators Metabotropic glutamate receptor modulators Glutamate
Glutamate
metabolism/transport modulators

v t e

Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptor
modulators

nAChRs

Agonists (and PAMs)

5-HIAA A-84,543 A-366,833 A-582,941 A-867,744 ABT-202 ABT-418 ABT-560 ABT-894 Acetylcholine Altinicline Anabasine Anatoxin-a AR-R17779 Bephenium hydroxynaphthoate Butinoline Butyrylcholine Carbachol Choline Cotinine Cytisine Decamethonium Desformylflustrabromine Dianicline Dimethylphenylpiperazinium Epibatidine Epiboxidine Ethanol
Ethanol
(alcohol) Ethoxysebacylcholine EVP-4473 EVP-6124 Galantamine GTS-21 Ispronicline Ivermectin JNJ-39393406 Levamisole Lobeline MEM-63,908 (RG-3487) Morantel Nicotine
Nicotine
(tobacco) NS-1738 PHA-543,613 PHA-709,829 PNU-120,596 PNU-282,987 Pozanicline Pyrantel Rivanicline RJR-2429 Sazetidine A SB-206553 Sebacylcholine SIB-1508Y SIB-1553A SSR-180,711 Suberyldicholine Suxamethonium
Suxamethonium
(succinylcholine) Suxethonium (succinyldicholine) TC-1698 TC-1734 TC-1827 TC-2216 TC-5214 TC-5619 TC-6683 Tebanicline Tribendimidine Tropisetron UB-165 Varenicline WAY-317,538 XY-4083

Antagonists (and NAMs)

18-MAC 18-MC α-Neurotoxins (e.g., α-bungarotoxin, α-cobratoxin, α-conotoxin, many others) ABT-126 Alcuronium Allopregnanolone Amantadine Anatruxonium AQW051 Atracurium Barbiturates
Barbiturates
(e.g., pentobarbital, sodium thiopental) BNC-210 Bungarotoxins (e.g., α-bungarotoxin, κ-bungarotoxin) Bupropion BW-A444 Candocuronium iodide
Candocuronium iodide
(chandonium iodide) Chlorisondamine Cisatracurium Coclaurine Coronaridine Curare Cyclopropane Dacuronium bromide Decamethonium Dehydronorketamine Desflurane Dextromethorphan Dextropropoxyphene Dextrorphan Diadonium DHβE Dihydrochandonium Dimethyltubocurarine
Dimethyltubocurarine
(metocurine) Dioscorine Dipyrandium Dizocilpine
Dizocilpine
(MK-801) Doxacurium Encenicline Enflurane Erythravine Esketamine Fazadinium Gallamine Gantacurium chloride Halothane Hexafluronium Hexamethonium
Hexamethonium
(benzohexonium) Hydroxybupropion Hydroxynorketamine Ibogaine Isoflurane Ketamine Kynurenic acid Laudanosine Laudexium
Laudexium
(laudolissin) Levacetylmethadol Levomethadone Malouetine ME-18-MC Mecamylamine Memantine Methadone Methorphan
Methorphan
(racemethorphan) Methyllycaconitine Metocurine Mivacurium Morphanol
Morphanol
(racemorphan) Neramexane Nitrous oxide Norketamine Pancuronium bromide Pempidine Pentamine Pentolinium Phencyclidine Pipecuronium bromide Progesterone Promegestone Radafaxine Rapacuronium bromide Reboxetine Rocuronium bromide Sevoflurane Stercuronium iodide Surugatoxin Thiocolchicoside Toxiferine Tramadol Trimetaphan camsilate
Trimetaphan camsilate
(trimethaphan camsylate) Tropeinium Tubocurarine Vanoxerine Vecuronium bromide Xenon

Precursors (and prodrugs)

Acetyl-coA Adafenoxate Choline
Choline
(lecithin) Citicoline Cyprodenate Dimethylethanolamine Glycerophosphocholine Meclofenoxate
Meclofenoxate
(centrophenoxine) Phosphatidylcholine Phosphatidylethanolamine Phosphorylcholine Pirisudanol

See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Acetylcholine
Acetylcholine
metabolism/tr

.