Editing Amyl nitrite

{{Short description|Chemical compound}}
{{Distinguish|Amyl nitrate}}
{{cs1 config|name-list-style=vanc}}
{{infobox drug
| Watchedfields      = changed
| verifiedrevid      = 451716663
| type               = 
| drug_name          = 
| image              = Amyl nitrite.svg
| image_class        = skin-invert-image
| width              = 175px
| alt                = Chemical structure of amyl nitrite
| image2             = Amyl-nitrite-3D-balls.png
| width2             = 200px
| alt2               = Ball-and-stick model of amyl nitrite
| IUPAC_name         = (3-methylbutyl) nitrite
| synonyms           = Isoamyl nitrite,<br/>Isopentyl nitrite,<br/>Nitramyl,<br/>3-methyl-1-nitrosooxybutane,<br/>Pentyl alcohol nitrite&nbsp;(ambiguous),<br/>''poppers'' (ambiguous, colloquial, slang)
| legal_AU           = [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 3|S3]] (Pharmacist only) / [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 4|S4]] (Prescription only)
| legal_AU_comment   = <ref>''[https://www.legislation.gov.au/F2024L01228 Therapeutic Goods (Poisons Standard—October 2024) Instrument 2024]'' (Cth). Schedule 3 "when in preparations for human therapeutic use and packaged in containers with child‑resistant closures"; schedule 4 otherwise.</ref>
| legal_UK           = [[Medicines Act 1968|Controlled Drug (Medicines Act 1968)]]
| legal_US           = Unscheduled [[Crime Control Act of 1990|(illegal under Crime Control Act of 1990)]]
| legal_DE           = Unscheduled (unauthorized sale and purchase illegal)
| legal_BR           = C1
| legal_BR_comment   = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2024-05-28 |title=RDC Nº 877 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 877 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-da-diretoria-colegiada-anvisa-n-877-de-28-de-maio-de-2024-562758149 |url-status=live |archive-url=https://web.archive.org/web/20240925040323/https://www.in.gov.br/en/web/dou/-/resolucao-da-diretoria-colegiada-anvisa-n-877-de-28-de-maio-de-2024-562758149 |archive-date=2024-09-25 |access-date=2024-09-25 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2024-05-28}}</ref>
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB01612
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 2691
| SMILES             = CC(C)CCON=O
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = 5N0U5TUC9Z
| PubChem            = 8053
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C5H11NO2/c1-5(2)3-4-8-6-7/h5H,3-4H2,1-2H3
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = OWFXIOWLTKNBAP-UHFFFAOYSA-N
| CAS_number         = 110-46-3
| CAS_number_Ref     = {{cascite|correct|CAS}}
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 7762
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D00517
| C                  = 5
| H                  = 11
| N                  = 1
| O                  = 2
| density            = 0.872
| solubility         = Slightly soluble
| melting_point      = 
| boiling_point      = 99
| ATC_prefix         = V03
| ATC_suffix         = AB22
<!-- | OtherCompounds = [[Nitroglycerine]]<br/>[[Isopentanol]]<br/>[[Butyl nitrite]]<br/>[[Isobutyl nitrite]]<br/> [[Ethyl nitrite]]<br/> [[Methyl nitrite]]<br/> [[Isopropyl nitrite]]<br/> [[Cyclohexyl nitrite]] -->}}

'''Amyl nitrite''' is a [[chemical compound]] with the [[chemical formula|formula]] C<sub>5</sub>H<sub>11</sub>ONO. A variety of isomers are known, but they all feature an [[Pentyl|amyl]] group attached to the [[nitrite]] functional group. The alkyl group (the amyl in this case) is unreactive and the chemical and biological properties are mainly due to the nitrite group. Like other [[alkyl nitrite]]s, amyl nitrite is bioactive in mammals, being a [[vasodilator]], which is the basis of its use as a prescription medicine.<ref>{{cite web |title=Amyl Nitrite (Inhalation Route) Description and Brand Names - Mayo Clinic |url=https://www.mayoclinic.org/drugs-supplements/amyl-nitrite-inhalation-route/description/drg-20061803 |access-date=2023-12-05 |website=www.mayoclinic.org}}</ref> As an inhalant, it also has a [[Psychoactive drug|psychoactive]] effect, which has led to its recreational use, with its smell being described as that of old socks or dirty feet.<ref>{{cite web|url=http://www.urban75.com/Drugs/drugamyl.html|title=Drugs - Amyl, Butyl or Isobutyl Nitrite, Nitrates, Poppers|work=urban75.com}}</ref> 
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It was first documented in 1844 and came into medical use in 1867.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=XXX |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PAXXX |language=en}}</ref>

==Uses==
* Amyl nitrite was historically employed medically to treat [[ischaemic heart disease|heart disease]]s as well as [[Angina pectoris|angina.]] 
* Amyl nitrite was sometimes used as an antidote for [[cyanide poisoning]].<ref name="detoxification48"/><ref>{{cite journal | vauthors = Mason DT, Braunwald E | title = The effects of nitroglycerin and amyl nitrite on arteriolar and venous tone in the human forearm | journal = Circulation | volume = 32 | issue = 5 | pages = 755–766 | date = November 1965 | pmid = 4954412 | doi = 10.1161/01.cir.32.5.755 | doi-access = free }}</ref> It was thought to act as an [[oxidant]], to induce the formation of [[methemoglobin]]. [[Methemoglobin]] in turn can sequester [[cyanide]] as cyanomethemoglobin.<ref>{{cite journal| title = Cyanide Antidotes: from Amyl Nitrite to Hydroxocobalamin – Which Antidote is Best?| vauthors = Vale JA | journal = [[Toxicology (journal)|Toxicology]]| year = 2001| volume = 168| issue = 1| pages = 37–38}}</ref> However, it has been replaced by [[hydroxocobalamin]] which had better efficacy,<ref>{{cite journal| vauthors = Hall AH, Saiers J, Baud F | title = Which cyanide antidote? | journal = Crit Rev Toxicol | date = 2009 | volume = 39 | issue = 7 | pages = 541–552 | pmid =  19650716| doi = 10.1080/10408440802304944 | doi-access = free }}</ref> and the use of amyl nitrite has been found to be ineffective and unscientific.<ref>{{cite journal| vauthors = Lavon O, Bentur Y | title = Does amyl nitrite have a role in the management of pre-hospital mass casualty cyanide poisoning? | journal = Clin Toxicol (Phila) | volume = 48 | issue = 6 | pages = 477–484 | date = July 2010 | pmid =  20653465| doi = 10.3109/15563650.2010.505573 | doi-access = free }}</ref>
*  Trace amounts are added to some [[perfumes]].<ref>{{cite web |url= https://pubchem.ncbi.nlm.nih.gov/compound/Amyl-nitrite#section=Use-and-Manufacturing |title=Amyl Nitrite Use and Manufacturing|work=PubChem | publisher = U.S. National Library of Medicine }}</ref>
* It is also used recreationally as an [[inhalant]] drug that induces a brief euphoric state, and when combined with other intoxicant stimulant drugs such as [[cocaine]] or [[MDMA]], the euphoric state intensifies and is prolonged. Once some stimulative drugs wear off, a common side effect is a period of [[Depression (mood)|depression]] or [[anxiety (mood)|anxiety]], colloquially called a "come down"; amyl nitrite is sometimes used to combat these negative after-effects. {{Citation needed|date=May 2025}}  This effect, combined with its dissociative effects, has led to its use as a recreational drug {{xref|(see: [[Poppers]])}}.<ref name="detoxification48">{{cite book | vauthors = Giannini AJ, Slaby AE, Giannini MC | title = The Handbook of Overdose and Detoxification Emergencies | location = New Hyde Park, NY. | publisher = Medical Examination Publishing Co. | date = 1982 | pages = 48–50 }}</ref>

==Nomenclature==
The term "amyl nitrite" encompasses several [[isomer]]s. In older literature, the common non-systematic name '''amyl''' was often used for the [[pentyl group]], where the amyl group is a [[Alkane#Linear alkanes|linear or normal (n)]] [[alkyl]] group, and the resulting amyl nitrite would have the structural formula CH<sub>3</sub>(CH<sub>2</sub>)<sub>3</sub>CH<sub>2</sub>ONO, also referred to as n-amyl nitrite.

A common form of amyl nitrite is the isomer with the formula (CH<sub>3</sub>)<sub>2</sub>CHCH<sub>2</sub>CH<sub>2</sub>ONO, which may be more specifically referred to as isoamyl nitrite.

The similarly named [[amyl nitrate]] has very different properties. At the same time, [[isopropyl nitrite]] has a similar structure and similar uses (also called 'poppers') but with worse side-effects.<ref>{{cite book | last=Cantrell | first=F.L. | title=Encyclopedia of Toxicology | chapter=Nitrite Inhalants | publisher=Elsevier | year=2014 | pages=530–531 | doi=10.1016/b978-0-12-386454-3.00042-7| isbn=9780123864550 }}</ref>

Amyl nitrite is sometimes referred to colloquially as ''banapple gas''.<ref>{{cite book| vauthors = Nordegren T |title=The A-Z Encyclopedia of Alcohol and Drug Abuse|date=2002|publisher=Brown Walker Press|isbn=158112404X|page=94|url=https://books.google.com/books?id=4yaGePenGKgC&q=%22A-Z+Encyclopedia+of+Alcohol+and+Drug+Abuse%22&pg=PA5|access-date=5 February 2017}}</ref>

==Synthesis and reactions==
Alkyl nitrites are prepared by the reaction of [[Alcohol (chemistry)|alcohol]]s with [[nitrous acid]]:<ref>{{OrgSynth | vauthors = Noyes WA |author-link=William A. Noyes |year=1943 |title=n-Butyl Nitrite |volume= |pages= |collvol=2 |collvolpages=108 |prep=CV2P0108}}</ref>

:ROH  +  HONO  →  RONO  +  H<sub>2</sub>O, where R = alkyl group

The reaction is called [[esterification]]. Synthesis of alkyl nitrites is, in general, straightforward and can be accomplished in home laboratories. A common procedure includes the dropwise addition of concentrated [[sulfuric acid]] to a cooled mixture of an aqueous sodium nitrite solution and an alcohol. The intermediately-formed stoichiometric mixture of nitrogen dioxide and nitric oxide then converts the alcohol to the alkyl nitrite, which, due to its low density, will form an upper layer that can be easily [[Decantation|decanted]] from the reaction mixture.

Isoamyl nitrite decomposes in the presence of base to give nitrite salts and the [[Amyl alcohol|isoamyl alcohol]]:
:C<sub>5</sub>H<sub>11</sub>ONO  +  NaOH  → C<sub>5</sub>H<sub>11</sub>OH  +  [[sodium nitrite|NaNO<sub>2</sub>]]

Amyl nitrite, like other alkyl nitrites, reacts with [[carbanion]]s to give [[oxime]]s.<ref>{{OrgSynth | vauthors = Chen YK, Jeon SJ, Walsh PJ, Nugent WA | title = (2S)-(−)-3-exo-(Morpholino)isoborneol ((−)-MIB) | volume = 82 | pages = 87 | year = 2005 | prep = v82p0087}}</ref>

Amyl nitrites are also useful as reagents in a modification of the [[Sandmeyer reaction]].  The reaction of the alkyl nitrite with an aromatic [[amine]] in a halogenated solvent produces a [[radical (chemistry)|radical]] aromatic species, this then frees a [[halogen]] atom from the solvent.  For the synthesis of [[Organoiodine compound|aryl iodide]]s [[diiodomethane]] is used,<ref>{{cite journal | vauthors = Smith WB, Ho OC | title = Application of the isoamyl nitrite-diiodomethane route to aryl iodides | journal = The Journal of Organic Chemistry | volume = 55 | pages = 2543–2545 | year = 1990 | doi = 10.1021/jo00295a056 | issue = 8 }}</ref><ref>{{cite journal | vauthors = Cornforth J, Kumar A, Stuart AS | title = Synthesis of substituted dibenzophospholes. Part 6. Preparation of symmetrical and non-symmetrical quaterphenyl intermediates | journal = Journal of the Chemical Society, Perkin Transactions 1 | page = 859 | year = 1987 | doi = 10.1039/P19870000859}}</ref> whereas [[bromoform]] is the solvent of choice for the synthesis of [[Organobromine compound|aryl bromide]]s.<ref>{{cite journal | vauthors = Cadogan JI, Roy DA, Smith DM | title = An alternative to the Sandmeyer reaction | journal = Journal of the Chemical Society C: Organic | page = 1249 | year = 1966 | doi = 10.1039/J39660001249}}</ref>

==Physiological effects==
[[File:An early container of Amyl Nitrite, Hunterian Museum, Glasgow.jpg|thumb|An early container of amyl nitrite, Hunterian Museum, Glasgow]]

Amyl nitrite, in common with other [[alkyl nitrites]],<ref>{{cite book | vauthors = Nickerson M, Parker JO, Lowry TP, Swenson EW | title = Isobutyl Nitrite and Related Compounds. | location = San Francisco California | publisher = PHARMEX | date = 1979 | url = http://www.virusmythpoppersmyth.org/isobutyl_nitrite_and_rela/files/IBNtextnpttypepad.pdf | archive-url = https://web.archive.org/web/20070927023207/http://www.virusmythpoppersmyth.org/isobutyl_nitrite_and_rela/files/IBNtextnpttypepad.pdf | archive-date=2007-09-27 | edition = 1st }}</ref> is a potent [[vasodilator]]; it expands [[blood vessel]]s, resulting in lowering of the [[blood pressure]]. Amyl nitrite may be used during cardiovascular stress testing in patients with suspected hypertrophic cardiomyopathy to cause vasodilation and thereby reduce [[afterload]] and provoke obstruction of blood flow towards the aorta from the ventricle by increasing the pressure gradient, thereby causing left ventricular outflow obstruction. Alkyl nitrites are a source of [[nitric oxide]], which signals for relaxation of the [[Cardiac muscle|involuntary muscles]]. Physical effects include decrease in blood pressure, headache, flushing of the face, increased heart rate, dizziness, and relaxation of involuntary muscles, especially the [[blood vessel]] walls and the [[internal anal sphincter|internal]] and [[external anal sphincter]]. There are no [[Drug withdrawal|withdrawal]] symptoms. [[Overdose]] symptoms include [[nausea]], [[emesis|vomiting]], [[hypotension]], [[hypoventilation]], [[dyspnea|shortness of breath]], and [[fainting]]. The effects set in very quickly, typically within a few seconds and disappear within a few minutes.  Amyl nitrite may also intensify the experience of [[synesthesia]].<ref>{{cite book | vauthors = Cytowic R | author-link1 = Richard Cytowic | title = [[The Man Who Tasted Shapes]] | date = 2003 | publisher = MIT Press | isbn = 978-0-262-53255-6 }}</ref> Amyl nitrite, when given as a medication for patients with angina, can also be administered as an ampule. The ampule is put in a gauze pad and then inhaled by the patient during an angina attack and repeated every fifteen minutes. However, oral dosing of amyl nitrite is ineffective due to poor absorption and extensive hepatic metabolism. Amyl nitrite has been widely replaced by [[Nitroglycerin (medication)|nitroglycerin]] for the treatment of acute angina.{{Citation needed|date=March 2025}}

== Toxicity ==
Although there are case reports of life-threatening toxicity involving unusually large amounts,<ref name="Modarai_2002">{{cite journal | vauthors = Modarai B, Kapadia YK, Kerins M, Terris J | title = Methylene blue: a treatment for severe methaemoglobinaemia secondary to misuse of amyl nitrite | journal = Emergency Medicine Journal | volume = 19 | issue = 3 | pages = 270–271 | date = May 2002 | pmid = 11971852 | pmc = 1725875 | doi = 10.1136/emj.19.3.270 }}</ref> typical inhaled doses of amyl nitrite are considered relatively safe.<ref>{{cite journal | vauthors = Nutt D, King LA, Saulsbury W, Blakemore C | title = Development of a rational scale to assess the harm of drugs of potential misuse | journal = Lancet | volume = 369 | issue = 9566 | pages = 1047–1053 | date = March 2007 | pmid = 17382831 | doi = 10.1016/S0140-6736(07)60464-4 | s2cid = 5903121 }}</ref><ref>{{cite web | vauthors = O'Malley MF, O'Malley R |date=May 2020|title=Volatile Nitrites|url=https://www.msdmanuals.com/en-gb/professional/special-subjects/recreational-drugs-and-intoxicants/volatile-nitrites | work = MSD Manual | publisher = 2023 Merck & Co., Inc. }}</ref> However, liquid amyl nitrite is highly toxic when ingested because of the dangerously high concentration it causes in the blood.<ref name="Toxbase">{{cite web |date=December 2018 |title=Amyl Nitrite |url= https://www.toxbase.org |access-date= September 29, 2020 |website=Toxbase |publisher=UK National Poisons Information Service}}</ref> Regardless of the form or route of administration, acute toxicity principally results when the nitrite oxidizes a significant proportion of hemoglobin in the blood without oxygen, forming methemoglobin, which cannot carry oxygen. Severe poisoning cases will progress to [[methemoglobinemia]], characterized by a blue-brown discoloration under the skin which could be mistaken for cyanosis.<ref name="Modarai_2002" /><ref name="Toxbase" /> Treatment with oxygen and intravenous methylene blue frustrates visual confirmation further as methylene blue itself is, as its name suggests, a blue dye; the patient's changes in different shades of blue notwithstanding, it is an effective antidote by way of catalyzing the production of the enzyme responsible for reducing the methemoglobin in the blood back to hemoglobin.

The discoloration does mean that regular near-infrared–based pulse oximetry becomes useless. More fundamentally, blood gas analysis on the whole has limited effectiveness, as the increased methemoglobin level increases the oxygen binding affinity of regular hemoglobin.<ref name="Modarai_2002" /> Therefore, the measurement of actual ratios and levels of methemoglobin and hemoglobin must accompany any blood gas partial pressure sample in these cases.

== In popular culture ==
The ''[[Columbo]]'' episode titled "[[Columbo (season 4)|Troubled Waters]]" (1974–1975) features amyl nitrite inhaled by the antagonist Hayden Danziger – played by [[Robert Vaughn]] – to help him feign a heart attack for his alibi. However, the episode consistently refers to the substance incorrectly as amyl nitrate.<ref name="20.">{{cite web |title=Episode review: Columbo Troubled Waters |url=https://columbophile.com/2018/09/29/episode-review-columbo-troubled-waters/ |website=Columbophile blog |date=29 September 2018 |access-date=8 April 2023}}</ref>

The 1978 [[Derek Jarman]] film ''[[Jubilee (1978 film)|Jubilee]]'' features a character named Amyl Nitrate (a misspelled reference to amyl nitrite).

The title of the 1993 song "[[Animal Nitrate]]" by English band [[Suede (band)|Suede]] is a pun on amyl nitrite, referencing its recreational use, although singer [[Brett Anderson]] has said the song has more to do with other drugs like [[MDMA|ecstasy]] and cocaine.<ref name="NME">{{cite journal |last=Mulvey |first=John |title=Latter-Day Nitrate Fever |journal=NME |date=20 February 1993 |pages=24}}</ref>

In the 1999 film ''[[Fight Club (film)|Fight Club]]'', the character Chloe, a terminally ill woman, mentions having a collection of amyl nitrite while openly discussing her unfulfilled desires at a cancer support group.

The punk band [[Amyl and the Sniffers]] reference recreational use of amyl nitrite in their name.<ref>{{cite news |date=2019-05-14 |title=Amyl and The Sniffers: 'It's just charmingly violent powerful fun' |language=en-GB |url=https://www.bbc.com/news/entertainment-arts-48177077 |access-date=2023-12-02}}</ref>

The [[Hunter S. Thompson]] book ''[[Fear and Loathing in Las Vegas]]'' sees amyl nitrite as one of the many drugs Raoul Duke packs for the trip to [[Las Vegas]], taking about two dozen ampules of it with him and usually justifying its usage by him and [[Oscar Zeta Acosta|Dr. Gonzo]] to other people around them by claiming it is for [[angina]].

In Season 1, Episode 9 of ''[[Bob's Burgers]]'', "[[Spaghetti Western and Meatballs]]", Gene guesses amyl nitrite for the A in the ABS program near the end of the episode.

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Kjonaas RA | title = Amyl: A Misunderstood Word | journal = Journal of Chemical Education | volume = 73 | page = 1127 | year = 1996 | doi = 10.1021/ed073p1127 | issue = 12| bibcode = 1996JChEd..73.1127K }} Editorial on the use of the word "amyl".
{{refend}}

{{Antidotes}}
{{Nitric oxide signaling}}

{{DEFAULTSORT:Amyl Nitrite}}
[[Category:Antianginals]]
[[Category:Antidotes]]
[[Category:Alkyl nitrites]]
[[Category:Muscle relaxants]]
[[Category:Vasodilators]]
[[Category:Isoamyl esters]]