Amyl nitrite
 | |
 | |
| Clinical data | |
|---|---|
| Other names | Isoamyl nitrite, Isopentyl nitrite, Nitramyl, 3-methyl-1-nitrosooxybutane, Pentyl alcohol nitrite (ambiguous), poppers(ambiguous, colloquial, slang) |
| ATC code | |
| Legal status | |
| Legal status |
|
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C5H11NO2 |
| Molar mass | 117.148g·mol−1 |
| 3D model (JSmol) | |
| Density | 0.872 g/cm3 |
| Boiling point | 99 °C (210 °F) |
| Solubility in water | Slightly soluble mg/mL (20 °C) |
| |
| |
| (verify) | |
Amyl nitriteis achemical compoundwith theformulaC5H11ONO. A variety of isomers are known, but they all feature anamylgroup attached to thenitritefunctional 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 otheralkyl nitrites,amyl nitrite is bioactive in mammals, being avasodilator,which is the basis of its use as a prescription medicine.[2]As an inhalant, it also has apsychoactiveeffect, which has led to its recreational use, with its smell being described as that of old socks or dirty feet.[3] It was first documented in 1844 and came into medical use in 1867.[4]
Uses
[edit]- Amyl nitrite was historically employed medically to treatheart diseasesas well asangina.
- Amyl nitrite was sometimes used as an antidote forcyanide poisoning.[5][6]It was thought to act as anoxidant,to induce the formation ofmethemoglobin.Methemoglobinin turn can sequestercyanideas cyanomethemoglobin.[7]However, it has been replaced byhydroxocobalaminwhich had better efficacy,[8]and the use of amyl nitrite has been found to be ineffective and unscientific[9]
- Amyl nitrite is used as acleaning agentandsolventin industrial and household applications. It replaceddichlorodifluoromethane('Freon-12'), an industrial chemical universally banned in 1996 due to damage to theozone layer,[10]as aprinted circuit boardcleaner.[citation needed]Trace amounts are added to someperfumes.[11]
- It is also used recreationally as aninhalantdrug that induces a brief euphoric state, and when combined with other intoxicant stimulant drugs such ascocaineorMDMA,the euphoric state intensifies and is prolonged. Once some stimulative drugs wear off, a common side effect is a period ofdepressionoranxiety,colloquially called a "come down"; amyl nitrite is sometimes used to combat these negative after-effects. This effect, combined with its dissociative effects, has led to its use as a recreational drug.[5]
Nomenclature
[edit]The term "amyl nitrite" encompasses severalisomers.In older literature, the common non-systematic nameamylwas often used for thepentyl group,where the amyl group is alinear or normal (n)alkylgroup, 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 namedamyl nitratehas very different properties. At the same time,isopropyl nitritehas a similar structure and similar uses (also called 'poppers') but with worse side-effects.[12]
Amyl nitrite is sometimes referred to colloquially asbanapple gas.[13]
Synthesis and reactions
[edit]Alkyl nitrites are prepared by the reaction ofalcoholswithnitrous acid:[14]
- ROH + HONO → RONO + H2O, where R = alkyl group
The reaction is calledesterification.Synthesis of alkyl nitrites is, in general, straightforward and can be accomplished in home laboratories. A common procedure includes the dropwise addition of concentratedsulfuric acidto 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 easilydecantedfrom the reaction mixture.
Isoamyl nitrite decomposes in the presence of base to give nitrite salts and theisoamyl alcohol:
- C5H11ONO + NaOH → C5H11OH +NaNO2
Amyl nitrite, like other alkyl nitrites, reacts withcarbanionsto giveoximes.[15]
Amyl nitrites are also useful as reagents in a modification of theSandmeyer reaction.The reaction of the alkyl nitrite with an aromaticaminein a halogenated solvent produces aradicalaromatic species, this then frees ahalogenatom from the solvent. For the synthesis ofaryl iodidesdiiodomethaneis used,[16][17]whereasbromoformis the solvent of choice for the synthesis ofaryl bromides.[18]
Physiological effects
[edit]
Amyl nitrite, in common with otheralkyl nitrites,[19]is a potentvasodilator;it expandsblood vessels,resulting in lowering of theblood pressure.Amyl nitrite may be used during cardiovascular stress testing in patients with suspected hypertrophic cardiomyopathy to cause vasodilation and thereby reduceafterloadand 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 ofnitric oxide,which signals for relaxation of theinvoluntary muscles.Physical effects include decrease in blood pressure, headache, flushing of the face, increased heart rate, dizziness, and relaxation of involuntary muscles, especially theblood vesselwalls and theinternalandexternal anal sphincter.There are nowithdrawalsymptoms.Overdosesymptoms includenausea,vomiting,hypotension,hypoventilation,shortness of breath,andfainting.The effects set in very quickly, typically within a few seconds and disappear within a few minutes. Amyl nitrite may also intensify the experience ofsynesthesia.[20]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 bynitroglycerinfor the treatment of acute angina.
Toxicity
[edit]Although there are case reports of life-threatening toxicity involving unusually large amounts,[21]typical inhaled doses of amyl nitrite are considered relatively safe.[22][23]However, liquid amyl nitrite is highly toxic when ingested because of the unsafely high concentration it causes in blood.[24]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 tomethemoglobinemia,characterized by a blue-brown discoloration under the skin which could be mistaken for cyanosis.[21][24]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.[21]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
[edit]TheColumboepisode 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.[25]
The 1978Derek JarmanfilmJubileefeatures a character named Amyl Nitrate (a misspelled reference to amyl nitrite).
The punk bandAmyl and the Sniffersreference recreational use of amyl nitrite in their name.[26]
TheHunter S. ThompsonbookFear and Loathing in Las Vegassees amyl nitrite as one of the many drugs Raoul Duke packs for the trip toLas 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's forangina.
References
[edit]- ^Anvisa(2024-05-28)."RDC Nº 877 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 877 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União.Archivedfrom the original on 2024-09-25.Retrieved2024-09-25.
- ^"Amyl Nitrite (Inhalation Route) Description and Brand Names - Mayo Clinic".www.mayoclinic.org.Retrieved2023-12-05.
- ^"Drugs - Amyl, Butyl or Isobutyl Nitrite, Nitrates, Poppers".urban75.com.
- ^Fischer J, Ganellin CR (2006).Analogue-based Drug Discovery.John Wiley & Sons. p. XXX.ISBN9783527607495.
- ^abGiannini AJ, Slaby AE, Giannini MC (1982).The Handbook of Overdose and Detoxification Emergencies.New Hyde Park, NY.: Medical Examination Publishing Co. pp. 48–50.
- ^Mason DT, Braunwald E (November 1965)."The effects of nitroglycerin and amyl nitrite on arteriolar and venous tone in the human forearm".Circulation.32(5): 755–766.doi:10.1161/01.cir.32.5.755.PMID4954412.
- ^Vale JA (2001). "Cyanide Antidotes: from Amyl Nitrite to Hydroxocobalamin – Which Antidote is Best?".Toxicology.168(1): 37–38.
- ^Hall AH, Saiers J, Baud F (2009)."Which cyanide antidote?".Crit Rev Toxicol.39(7): 541–552.doi:10.1080/10408440802304944.PMID19650716.
- ^Lavon O, Bentur Y (July 2010)."Does amyl nitrite have a role in the management of pre-hospital mass casualty cyanide poisoning?".Clin Toxicol (Phila).48(6): 477–484.doi:10.3109/15563650.2010.505573.PMID20653465.
- ^"Dichlorodifluoromethane".LearnChemistry.Royal Society of Chemistry.
- ^"Amyl Nitrite Use and Manufacturing".PubChem.U.S. National Library of Medicine.
- ^Cantrell F (2014). "Nitrite Inhalants".Encyclopedia of Toxicology.Elsevier. pp. 530–531.doi:10.1016/b978-0-12-386454-3.00042-7.ISBN9780123864550.
- ^Nordegren T (2002).The A-Z Encyclopedia of Alcohol and Drug Abuse.Brown Walker Press. p. 94.ISBN158112404X.Retrieved5 February2017.
- ^Noyes WA(1943)."n-Butyl Nitrite".Organic Syntheses;Collected Volumes,vol. 2, p. 108.
- ^Chen YK, Jeon SJ, Walsh PJ, Nugent WA (2005)."(2S)-(−)-3-exo-(Morpholino)isoborneol ((−)-MIB)".Organic Syntheses.82:87.
- ^Smith WB, Ho OC (1990). "Application of the isoamyl nitrite-diiodomethane route to aryl iodides".The Journal of Organic Chemistry.55(8): 2543–2545.doi:10.1021/jo00295a056.
- ^Cornforth J, Kumar A, Stuart AS (1987). "Synthesis of substituted dibenzophospholes. Part 6. Preparation of symmetrical and non-symmetrical quaterphenyl intermediates".Journal of the Chemical Society, Perkin Transactions 1:859.doi:10.1039/P19870000859.
- ^Cadogan JI, Roy DA, Smith DM (1966). "An alternative to the Sandmeyer reaction".Journal of the Chemical Society C: Organic:1249.doi:10.1039/J39660001249.
- ^Nickerson M, Parker JO, Lowry TP, Swenson EW (1979).Isobutyl Nitrite and Related Compounds(PDF)(1st ed.). San Francisco California: PHARMEX. Archived fromthe original(PDF)on 2007-09-27.
- ^Cytowic R(2003).The Man Who Tasted Shapes.MIT Press.ISBN978-0-262-53255-6.
- ^abcModarai B, Kapadia YK, Kerins M, Terris J (May 2002)."Methylene blue: a treatment for severe methaemoglobinaemia secondary to misuse of amyl nitrite".Emergency Medicine Journal.19(3): 270–271.doi:10.1136/emj.19.3.270.PMC1725875.PMID11971852.
- ^Nutt D, King LA, Saulsbury W, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse".Lancet.369(9566): 1047–1053.doi:10.1016/S0140-6736(07)60464-4.PMID17382831.S2CID5903121.
- ^O'Malley MF, O'Malley R (May 2020)."Volatile Nitrites".MSD Manual.2023 Merck & Co., Inc.
- ^ab"Amyl Nitrite".Toxbase.UK National Poisons Information Service. December 2018.RetrievedSeptember 29,2020.
- ^"Episode review: Columbo Troubled Waters".Columbophile blog.29 September 2018.Retrieved8 April2023.
- ^"Amyl and The Sniffers: 'It's just charmingly violent powerful fun'".2019-05-14.Retrieved2023-12-02.
Further reading
[edit]- Kjonaas RA (1996). "Amyl: A Misunderstood Word".Journal of Chemical Education.73(12): 1127.Bibcode:1996JChEd..73.1127K.doi:10.1021/ed073p1127.Editorial on the use of the word "amyl".