:Amyl nitrite

• Amyl nitrite was historically employed medically to treat heart diseases as well as angina.
• Amyl nitrite was sometimes used as an antidote for cyanide poisoning.{{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 }} It was thought to act as an oxidant, to induce the formation of methemoglobin. Methemoglobin in turn can sequester cyanide as cyanomethemoglobin.{{cite journal| title = Cyanide Antidotes: from Amyl Nitrite to Hydroxocobalamin – Which Antidote is Best?| vauthors = Vale JA | journal = Toxicology| year = 2001| volume = 168| issue = 1| pages = 37–38}} However, it has been replaced by hydroxocobalamin which had better efficacy,{{cite journal| vauthors = Hall AH, Saiers J, Baud F | title = Which cyanide antidote?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 }} and the use of amyl nitrite has been found to be ineffective and unscientific.{{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 }}
• Trace amounts are added to some perfumes.{{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 }}
• 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 or 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)}}.{{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 }}

The term "amyl nitrite" encompasses several isomers. In older literature, the common non-systematic name amyl was often used for the pentyl group, where the amyl group is a linear or normal (n) alkyl group, and the resulting amyl nitrite would have the structural formula CH₃(CH₂)₃CH₂ONO, also referred to as n-amyl nitrite.

A common form of amyl nitrite is the isomer with the formula (CH₃)₂CHCH₂CH₂ONO, 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.{{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 }}

Amyl nitrite is sometimes referred to colloquially as banapple gas.{{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}}

Alkyl nitrites are prepared by the reaction of alcohols with nitrous acid:{{OrgSynth | vauthors = Noyes WA |author-link=William A. Noyes |year=1943 |title=n-Butyl Nitrite |volume= |pages= |collvol=2 |collvolpages=108 |prep=CV2P0108}}

:ROH + HONO → RONO + H₂O, 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 decanted from the reaction mixture.

Isoamyl nitrite decomposes in the presence of base to give nitrite salts and the isoamyl alcohol:

:C₅H₁₁ONO + NaOH → C₅H₁₁OH + NaNO₂

Amyl nitrite, like other alkyl nitrites, reacts with carbanions to give oximes.{{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}}

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 aromatic species, this then frees a halogen atom from the solvent. For the synthesis of aryl iodides diiodomethane is used,{{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 }}{{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}} whereas bromoform is the solvent of choice for the synthesis of aryl bromides.{{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}}

File:An early container of Amyl Nitrite, Hunterian Museum, Glasgow.jpg

Amyl nitrite, in common with other alkyl nitrites,{{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 }} is a potent vasodilator; it expands blood vessels, 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 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 and external anal sphincter. There are no withdrawal symptoms. Overdose symptoms include nausea, vomiting, hypotension, hypoventilation, 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.{{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 }} 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 for the treatment of acute angina.{{Citation needed|date=March 2025}}

Although there are case reports of life-threatening toxicity involving unusually large amounts,{{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 }} typical inhaled doses of amyl nitrite are considered relatively safe.{{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 }}{{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. }} However, liquid amyl nitrite is highly toxic when ingested because of the dangerously high concentration it causes in the blood.{{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}} 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. 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. Therefore, the measurement of actual ratios and levels of methemoglobin and hemoglobin must accompany any blood gas partial pressure sample in these cases.

The Columbo episode titled "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.{{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}}

The 1978 Derek Jarman 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 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 ecstasy and cocaine.{{cite journal |last=Mulvey |first=John |title=Latter-Day Nitrate Fever |journal=NME |date=20 February 1993 |pages=24}}

In the 1999 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.{{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}}

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 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.

{{Reflist}}

{{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".

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{{Antidotes}}

{{Nitric oxide signaling}}

{{DEFAULTSORT:Amyl Nitrite}}

Category:Antianginals

Category:Antidotes

Category:Alkyl nitrites

Category:Muscle relaxants

Category:Vasodilators

Category:Isoamyl esters