receptor channel. however, while gabaa receptor currents are increased by barbiturates (and other general anesthetics), 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 anesthetic concentrations of both thiopental and pentobarbital. such findings implicate (non-gaba-ergic) ligand-gated ion channels, e.g. the neuronal nachr channel, in mediating some of the (side) effects of barbiturates. this is the mechanism responsible for the (mild to moderate) anesthetic effect of barbiturates in high doses when used in anesthetic concentration. interactions drug interactions with barbiturates are: alcohol opioids alprazolam anticoagulants antihistamines atazanavir birth-control pills boceprevir clonazepam caution medications such as opioids, benzodiazepines alcohol asthma kidney or liver problems heart disease substance use disorder depression history of suicidal thoughts history barbituric acid was first synthesized 27 november 1864, by german chemist adolf von baeyer. this was done by condensing urea with diethyl malonate. 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. another story was barbiturate was invented on the feast day of st. barbara. another story holds that baeyer synthesized the substance from the collected urine of a munich waitress named barbara. no substance of medical value was discovered, however, until 1903 when two german scientists working at bayer, emil fischer and joseph von mering, discovered that barbital was very effective in putting dogs to sleep. barbital was then marketed by bayer under the trade name veronal. it is said that mering proposed this name because the most peaceful place he knew was the italian city of verona. it was not until the 1950s that the behavioral disturbances and physical dependence potential of barbiturates became recognized. 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 and z-drugs such as zolpidem, zaleplon and eszopiclone for sleep. the final class of barbiturates are known as long-acting barbiturates (the most notable one being phenobarbital, which has a half-life of roughly 92 hours). this class of barbiturates is used almost exclusively as anticonvulsants, although on rare occasions they are prescribed for daytime sedation. barbiturates in this class are not used for insomnia, because, owing to their extremely long half-life, patients would awake with a residual "hang-over" effect and feel groggy. barbiturates can in most cases be used either as the free acid or as salts of sodium, calcium, potassium, magnesium, lithium, etc. codeine- and dionine-based salts of barbituric acid have been developed. in 1912, bayer introduced another barbituric acid derivative, phenobarbital, under the trade name luminal, as a sedative–hypnotic. society and culture legal status 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 physicians prescribing high doses to unknowing patients through the 1950s and 1960s. in the late 1950s and 1960s, an increasing number of published reports of barbiturate overdoses and dependence problems led physicians to reduce 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 on list i. there is a small group of list ii drugs for which physicians 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 of 1970 classified most barbiturates as controlled substances—and they remain so as of september 2020. 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" (all other barbiturates) were designated as being schedule iii. under the original csa, no barbiturates were placed in schedule i, ii, or v; however, amobarbital, pentobarbital, and secobarbital are schedule ii controlled substances unless they are in a suppository dosage form. in 1971, the 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, 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". 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 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. 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. other effects of barbiturate intoxication include drowsiness, lateral and vertical nystagmus, slurred speech and ataxia, decreased anxiety, and loss of inhibitions. 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. often polysubstance use occurs and barbiturates are consumed with or substituted by other available substances, most commonly alcohol. people who use substances tend to prefer short-acting and intermediate-acting barbiturates. 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, barbies, bluebirds, dolls, wallbangers, yellows, downers, goofballs, sleepers, 'reds & blues', and tooties. examples generic structure of a barbiturate, including numbering scheme barbiturates short name r1 r2 iupac name duration of action allobarbitalch2chch2ch2chch25,5-diallylbarbiturate short-acting amobarbitalch2ch3(ch2)2ch(ch3)25-ethyl-5-isopentyl-barbiturate intermediate-acting aprobarbitalch2chch2ch(ch3)25-allyl-5-isopropyl-barbiturate intermediate-acting alphenalch2chch2c6h55-allyl-5-phenyl-barbiturate intermediate-acting barbitalch2ch3ch2ch35,5-diethylbarbiturate long-acting brallobarbitalch2chch2ch2cbrch25-allyl-5-(2-bromo-allyl)-barbiturate short-acting pentobarbitalch2ch3ch ch3(ch2)2ch35-ethyl-5-(1-methylbutyl)-barbiturate short-acting phenobarbitalch2ch3c6h55-ethyl-5-phenylbarbiturate long-acting primidone ch2ch3 c6h5 5-ethyl-5-phenyl-1,3-diazinane-4,6-dione (it lacks oxygen at #2 position of generic barbiturate structure) long-acting secobarbitalch2chch2chch3(ch2)2ch35--5-prop-2-enyl-barbiturate; 5-allyl-5--barbiturate short-acting thiopental ch2ch3 chch3(ch2)2ch3 5-ethyl-5-(1-methylbutyl)-2-thiobarbiturate (the oxygen at #2 position is replaced by a sulfur) ultrashort-acting thiopental is a barbiturate with one of the c=o double bonds (with the carbon being labelled 2 in the adjacent diagram) replaced with a c=s double bond, r1 being ch2ch3 (ethyl) and r3) being ch(ch3)ch2ch2ch3 (sec-pentyl). thiopental is no longer available in the united states.