Amobarbital

{{Short description|Barbiturate}} {{More citations needed|date=January 2026}} {{Infobox drug | Watchedfields = changed | class = Barbiturate | verifiedrevid = 464364523 | IUPAC_name = 5-ethyl-5-(3-methylbutyl)-1,3-diazinane-2,4,6-trione | image = Amobarbital.svg | image_class = skin-invert-image | width = 120 | image2 = Amobarbital ball-and-stick.png | image_class2 = bg-transparent | width2 = 200  | tradename = | Drugs.com = {{drugs.com|CONS|amobarbital}} | pregnancy_category = | legal_BR = B1 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}</ref> | legal_CA = Schedule IV | legal_DE = Anlage III | legal_US = Schedule II | legal_US_comment = / Schedule III | legal_UK = Class B | legal_UN = P III | legal_status = SE: Förteckning IV | licence_US = Amobarbital | routes_of_administration = By mouth, intramuscular, intravenous, rectal  | bioavailability = | metabolism = Hepatic | elimination_half-life = 8–42 hours | excretion = Renal  | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 57-43-2 | CAS_supplemental = 64-43-7 (sodium salt) | ATC_prefix = N05 | ATC_suffix = CA02 | ATC_supplemental = | PubChem = 2164 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01351 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 2079 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = GWH6IJ239E | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00555 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 2673 | ChEMBL_Ref = {{ebicite|correct|EBI}} | synonyms = Amylobarbitone, sodium amytal | ChEMBL = 267894  | C = 11 | H = 18 | N = 2 | O = 3 | smiles = O=C1NC(=O)NC(=O)C1(CCC(C)C)CC | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C11H18N2O3/c1-4-11(6-5-7(2)3)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VIROVYVQCGLCII-UHFFFAOYSA-N }}

'''Amobarbital''' (formerly known as '''amylobarbitone''' or '''sodium amytal''' as the soluble sodium salt) is a drug that is a barbiturate derivative. It has sedative-hypnotic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923. It is considered a short to intermediate acting barbiturate.

If amobarbital is taken for extended periods of time, physical and psychological dependence can develop. Amobarbital withdrawal mimics delirium tremens and may be life-threatening. Amobarbital was manufactured by Eli Lilly and Company in the United States under the brand name '''Amytal''' in bright blue bullet shaped capsules (known as Pulvules) or pink tablets (known as Diskets)<ref>{{Cite journal|last=Winek|first=Charles L.|date=1965-02-01|title=Dosage Form Names and Product Identification|url=https://academic.oup.com/ajhp/article/22/2/82/5212972|journal=American Journal of Health-System Pharmacy|language=en|volume=22|issue=2|pages=84|doi=10.1093/ajhp/22.2.82|issn=1079-2082|url-access=subscription}}</ref> containing 50, 100, or 200 milligrams of the drug. The drug was also manufactured generically.{{Citation needed|date=January 2026}}

Amobarbital was widely misused, known as "Blue Heavens" on the street. Amytal, as well as Tuinal, a combination drug containing equal quantities of secobarbital and amobarbital, were both manufactured by Eli Lilly until the late 1990s. However, as the popularity of benzodiazepines increased, prescriptions for these medications became increasingly rare beginning in the mid to late 1980s.{{Citation needed|date=January 2026}}

==Pharmacology== In an ''in vitro'' study in rat thalamic slices, amobarbital worked by activating GABA<sub>A</sub> receptors, which decreased input resistance, depressed burst and tonic firing, especially in ventrobasal and intralaminar neurons, while at the same time increasing burst duration and mean conductance at individual chloride channels; this increased both the amplitude and decay time of inhibitory postsynaptic currents.<ref>{{cite journal | vauthors = Kim HS, Wan X, Mathers DA, Puil E | title = Selective GABA-receptor actions of amobarbital on thalamic neurons | journal = British Journal of Pharmacology | volume = 143 | issue = 4 | pages = 485–94 | date = October 2004 | pmid = 15381635 | pmc = 1575418 | doi = 10.1038/sj.bjp.0705974 }}</ref>

Amobarbital has been used in a study to inhibit mitochondrial electron transport in the rat heart in an attempt to preserve mitochondrial function following reperfusion.<ref>{{cite journal | vauthors = Stewart S, Lesnefsky EJ, Chen Q | title = Reversible blockade of electron transport with amobarbital at the onset of reperfusion attenuates cardiac injury | journal = Translational Research | volume = 153 | issue = 5 | pages = 224–31 | date = May 2009 | pmid = 19375683 | doi = 10.1016/j.trsl.2009.02.003 }}</ref>

A 1988 study found that amobarbital increases benzodiazepine receptor binding ''in vivo'' with less potency than secobarbital and pentobarbital (in descending order), but greater than phenobarbital and barbital (in descending order).<ref>{{cite journal | vauthors = Miller LG, Deutsch SI, Greenblatt DJ, Paul SM, Shader RI | title = Acute barbiturate administration increases benzodiazepine receptor binding in vivo | journal = Psychopharmacology | volume = 96 | issue = 3 | pages = 385–90 | year = 1988 | pmid = 2906155 | doi = 10.1007/BF00216067 | s2cid = 29934652 }}</ref> (Secobarbital > pentobarbital > ''amobarbital'' > phenobarbital > barbital)

It has an {{LD50}} in mice of 212{{nbsp}}mg/kg s.c.{{Citation needed|date=November 2011}}

==Metabolism== Amobarbital undergoes both hydroxylation to form 3'-hydroxyamobarbital,<ref>{{cite journal | vauthors = Maynert EW | title = The alcoholic metabolites of pentobarbital and amobarbital in man | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 150 | issue = 1 | pages = 118–21 | date = October 1965 | pmid = 5855308 }}</ref> and N-glucosidation<ref>{{cite journal | vauthors = Tang BK, Kalow W, Grey AA | title = Amobarbital metabolism in man: N-glucoside formation | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 21 | issue = 1 | pages = 45–53 | date = July 1978 | pmid = 684279 }}</ref> to form 1-(beta-D-glucopyranosyl)-amobarbital.<ref>{{cite journal | vauthors = Soine PJ, Soine WH | title = High-performance liquid chromatographic determination of the diastereomers of 1-(beta-D-glucopyranosyl)amobarbital in urine | journal = Journal of Chromatography | volume = 422 | pages = 309–14 | date = November 1987 | pmid = 3437019 | doi = 10.1016/0378-4347(87)80468-1 }}</ref>

==Indications== ===Approved=== * Anxiety{{Citation needed|date=January 2026}} * Epilepsy{{Citation needed|date=January 2026}} * Insomnia{{Citation needed|date=January 2026}} * Wada test<ref>{{Citation |title=The Sodium Amytal (Wada) Test: Procedural and Interpretative Considerations |date=1998-01-01 |work=Handbook of Neurolinguistics |pages=189–203 |url=https://www.sciencedirect.com/science/chapter/edited-volume/abs/pii/B9780126660555500162 |access-date=2026-05-19 |publisher=Academic Press |language=en-US}}</ref>

===Unapproved/off-label=== When given slowly by an intravenous route, sodium amobarbital has a reputation for acting as a so-called truth serum. Under the influence, a person will divulge information that under normal circumstances they would block. This was most likely due to loss of inhibition. As such, the drug was first employed clinically by William Bleckwenn at the University of Wisconsin to circumvent inhibitions in psychiatric patients.<ref>{{ cite journal | vauthors = Bleckwenn WJ | year = 1930 | title = Sodium amytal in certain nervous and mental conditions | journal = Wisconsin Medical Journal | volume = 29 | pages = 693–696 }}</ref> The use of amobarbital as a truth serum has lost credibility due to the discovery that a subject can be coerced into having a "false memory" of the event.<ref name="Stocks">{{cite journal | vauthors = Stocks JT | title = Recovered memory therapy: a dubious practice technique | journal = Social Work | volume = 43 | issue = 5 | pages = 423–36 | date = September 1998 | pmid = 9739631 | doi = 10.1093/sw/43.5.423 }} {{subscription required}}</ref>

The drug may be used intravenously to interview patients with catatonic mutism, sometimes combined with caffeine to prevent sleep.<ref>{{cite journal | vauthors = McCall WV | title = The addition of intravenous caffeine during an amobarbital interview | journal = Journal of Psychiatry & Neuroscience | volume = 17 | issue = 5 | pages = 195–7 | date = November 1992 | pmid = 1489761 | pmc = 1188455 }}</ref>

It was used by the United States Armed Forces during World War II in an attempt to treat shell shock and return soldiers to the front-line duties.<ref>{{cite web |url=https://www.pbs.org/wgbh/amex/bulge/filmmore/pt.html |work=Battle of the Bulge - program transcript |title=Use of sodium amytal during WWII |quote=Ben Kimmelman, Captain, 28th Infantry: The assumptions were that this would have some kind of cathartic effect, the sodium amytal, which the men called ''blue 88's.'' You know, the most effective artillery piece of the Germans was the 88 and this was ''blue 88s'', because the sodium amytal was a blue tablet. |publisher=PBS |access-date=2017-08-24 |archive-url=https://web.archive.org/web/20090314070438/http://www.pbs.org/wgbh/amex/bulge/filmmore/pt.html |archive-date=2009-03-14 |url-status=dead }}</ref> This use has since been discontinued as the powerful sedation, cognitive impairment, and dis-coordination induced by the drug greatly reduced soldiers' usefulness in the field.{{Citation needed|date=January 2026}}

==Contraindications== {{Unreferenced section|date=January 2026}}[[File:TruthSerum.jpg|right|thumb|A vial of Amytal sodium]]

The following drugs should be avoided when taking amobarbital:{{Citation needed|date=January 2026}} * Antiarrhythmics, such as verapamil and digoxin * Antiepileptics, such as phenobarbital or carbamazepine * Antihistamines, such as doxylamine and clemastine * Antihypertensives, such as atenolol and propranolol * Ethanol * Benzodiazepines, such as diazepam, clobazam, clonazepam, nitrazepam, alprazolam, or lorazepam * Chloramphenicol * Chlorpromazine * Cyclophosphamide * Ciclosporin * Digitoxin * Doxorubicin * Doxycycline * Methoxyflurane * Metronidazole * Narcotic analgesics, such as morphine and oxycodone * Quinine * Steroids, such as prednisone and cortisone * Theophylline * Warfarin

==Interactions== Amobarbital has been known to decrease the effects of hormonal birth control.<ref>{{cite web | url=https://www.mskcc.org/pdf/cancer-care/patient-education/amobarbital-01 | title=Amobarbital | Memorial Sloan Kettering Cancer Center }}</ref>

==Overdose== {{Unreferenced section|date=January 2026}} Some side effects of overdose include confusion (severe); decrease in or loss of reflexes; drowsiness (severe); fever; irritability (continuing); low body temperature; poor judgment; shortness of breath or slow or troubled breathing; slow heartbeat; slurred speech; staggering; trouble in sleeping; unusual movements of the eyes; weakness (severe). Severe overdose may result in death without intervention.

==Chemistry== class=skin-invert-image|800px

Amobarbital (5-ethyl-5-isoamylbarbituric acid), like all barbiturates, is synthesized by reacting malonic acid derivatives with urea derivatives. In particular, in order to make amobarbital, α-ethyl-α-isoamylmalonic ester is reacted with urea (in the presence of sodium ethoxide).<ref>{{ cite patent | country = GB | status = patent | number = 191008 | gdate = 1923-10-25 | inventor = Layraud E | title = The manufacture of unsymmetrical c.c.-dialkylbarbituric acids }}</ref><ref>{{ cite patent | country = US | status = patent | number = 1856792 | gdate = 1932-05-03 | inventor = Shonle HA | title = Anhydrous alkali salts of 5,5-di-aliphatic-substituted barbituric acids and processes of producing them }}</ref>

==Society and culture== On the night of August 28, 1951, the housekeeper of actor Robert Walker found him to be in an emotional state. She called Walker's psychiatrist who arrived and administered amobarbital for sedation. Walker was allegedly drinking prior to his emotional outburst, and it is believed the combination of amobarbital and alcohol resulted in a severe reaction. As a result, he passed out and stopped breathing, and all efforts to resuscitate him failed. Walker died at 32 years old.{{Citation needed|date=January 2026}}

The British actor and comedian Tony Hancock killed himself in Australia in 1968 using the drug in combination with alcohol.{{Citation needed|date=January 2026}}

Eli Lilly manufactured amobarbital under the brand name Amytal until it was discontinued in the 1980s and replaced largely by the benzodiazepine family of drugs. Amytal was also widely abused. Street names for amobarbital include "blues", "blue angels", "blue birds", "blue devils", and "blue heavens" due to their blue capsule.<ref>{{cite web|url=http://www.memidex.com/blue-devils+amobarbital|title=blue devils (amobarbital) - Memidex dictionary/thesaurus|work=www.memidex.com}}</ref>

==See also== * Blue 88 * Depressant

==Notes== {{Reflist}}

Category:Hypnotics Category:Barbiturates Category:German inventions Category:Drugs developed by Eli Lilly and Company Category:Substances discovered in the 1920s