Acetylcysteine: Difference between revisions

{{Short description|Medication used to treat overdose of paracetamol}}

{{Use dmy dates|date=March 2023}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 443366456

| image = Acetylcysteine2.svg

| width = 125

| alt =

| image2 = Acetylcysteine-from-xtal-3D-bs-17.png

| width2 =

| alt2 =

| drug_name =

| caption =

<!-- Clinical data -->

| pronounce = {{IPAc-en|ə|ˌ|s|iː|t|əl|ˈ|s|ɪ|s|t|iː|n}} and similar ({{IPAc-en|ə|ˌ|s|ɛ|t|əl|-|,_|ˌ|æ|s|ᵻ|t|əl|-|,_|-|t|iː|n}})

| tradename = ACC 200, Acetadote, Fluimucil, Mucomyst, others

| Drugs.com = {{drugs.com|monograph|acetylcysteine}}

| MedlinePlus =

| licence_EU = <!-- EMA requires brand name -->

| DailyMedID = Acetylcysteine

| licence_US =

| pregnancy_AU = B2

| routes_of_administration = [[By mouth]], [[intravenous]], [[Inhalation administration|inhalation]]

| ATC_prefix = R05

| ATC_suffix = CB01

| ATC_supplemental = {{ATC|S01|XA08}} {{ATC|V03|AB23}}

| legal_AU = S4

| legal_AU_comment = <ref>[http://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=121503&agid=%28PrintDetailsPublic%29&actionid=1 DBL ACETYLCYSTEINE injection concentrate acetylcysteine 2 g/ 10 mL injection ampoule]</ref><ref>{{cite web | url=http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2018-PI-01811-1 | title=TGA eBS - Product and Consumer Medicine Information Licence }}</ref><ref>{{cite web | title=Acetylcysteine (Omegapharm) | date=30 November 2022 | url=https://www.healthdirect.gov.au/medicines/brand/amt,26341000036106/acetylcysteine-omegapharm | access-date=29 December 2022 | work = Healthdirect Australia }}</ref>

| legal_BR =

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_NZ = Prescription only

| legal_UK = POM

| legal_UK_comment = <ref>{{cite web | title=Acepiro 600 mg effervescent tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=30 August 2022 | url=https://www.medicines.org.uk/emc/product/13849/smpc | access-date=29 December 2022}}</ref>

| legal_US = Rx-only

| legal_US_comment = <ref name="Acetadote FDA label">{{cite web | title=Acetadote- acetylcysteine injection, solution | website=DailyMed | date=1 October 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=472f158a-5ab9-4308-8e49-1116e6ea3d39 | access-date=29 December 2022}}</ref>

<!-- Pharmacokinetic data -->

| bioavailability = 10% (Oral)<ref>{{cite book | vauthors = Stockley RA | title = Chronic Obstructive Pulmonary Disease a Practical Guide to Management. | date = 2008 | publisher = John Wiley & Sons | location = Chichester | isbn = 9780470755280 | page = 750 | url = https://books.google.com/books?id=y9li1geShyYC&pg=PA750 | url-status = live | archive-url = https://web.archive.org/web/20170908143219/https://books.google.com/books?id=y9li1geShyYC&pg=PA750 | archive-date = 8 September 2017 }}</ref>

| protein_bound = 50 to 83%<ref name=AHFS2015/>

| metabolism = [[Liver]]<ref name=AHFS2015/>

| elimination_half-life = 5.6 hours<ref name="Acetadote FDA label" />

| excretion = Kidney (30%),<ref name=AHFS2015/> faecal (3%)

<!-- Identifiers -->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 616-91-1

| CAS_supplemental =

| PubChem = 12035

| IUPHAR_ligand =

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB06151

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 11540

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00221

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 28939

| synonyms = ''N''-acetylcysteine; ''N''-acetyl-<small>L</small>-cysteine; NALC; NAC

<!-- Chemical data -->

| IUPAC_name = (2''R'')-2-acetamido-3-sulfanylpropanoic acid<ref>{{cite web|title=<small>L</small>-Cysteine, ''N''-acetyl- — Compound Summary|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=581|work=PubChem|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine |access-date=9 January 2012|date=25 March 2005|at=Identification|url-status=live|archive-url=https://web.archive.org/web/20140112235508/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=581|archive-date=12 January 2014}}</ref>

| C=5 | H=9 | N=1 | O=3 | S=1

| smiles = C/C(=N/[C@@H](CS)C(=O)O)/O

| StdInChI_comment =

| StdInChI = 1S/C5H9NO3S/c1-3(7)6-4(2-10)5(8)9/h4,10H,2H2,1H3,(H,6,7)(H,8,9)/t4-/m0/s1

| StdInChIKey = PWKSKIMOESPYIA-BYPYZUCNSA-N

| density =

| melting_point = 109

| melting_high = 110

| melting_notes =<ref name=sial/>

| boiling_point =

| boiling_notes =

| solubility =

| specific_rotation = +5° (c = 3% in water)<ref name=sial/>

<!-- Definition and uses -->

'''Acetylcysteine''', also known as '''''N''-acetylcysteine''' ('''NAC'''), not to be confused with [[Acetylcarnosine|N-Acetylcarnosine]], which is also abbreviated "NAC," is a [[medication]] that is used to treat [[paracetamol overdose]] and to loosen thick [[mucus]] in individuals with chronic bronchopulmonary disorders like [[pneumonia]] and [[bronchitis]].<ref name=AHFS2015>{{cite web|title=Acetylcysteine|url=https://www.drugs.com/monograph/acetylcysteine.html|publisher=The American Society of Health-System Pharmacists|access-date=22 August 2015|url-status=live|archive-url=https://web.archive.org/web/20150923231013/http://www.drugs.com/monograph/acetylcysteine.html|archive-date=23 September 2015}}</ref> It has been used to treat [[bezoars|lactobezoar]] in infants. It can be taken [[Intravenous therapy|intravenously]], by mouth, or inhaled as a mist.<ref name=AHFS2015/> Some people use it as a [[dietary supplement]].<ref>{{cite book|vauthors=Talbott SM|title=A Guide to Understanding Dietary Supplements|date=2012|publisher=Routledge|isbn=9781136805707|page=469|url=https://books.google.com/books?id=9ZZrW_j9XrcC&pg=PA469|url-status=live|archive-url=https://web.archive.org/web/20170908143219/https://books.google.com/books?id=9ZZrW_j9XrcC&pg=PA469|archive-date=8 September 2017}}</ref><ref>{{cite web|title=Cysteine|url=http://www.umm.edu/health/medical/altmed/supplement/cysteine|website=University of Maryland Medical Center|access-date=23 June 2017|url-status=live|archive-url=https://web.archive.org/web/20170701184417/http://www.umm.edu/health/medical/altmed/supplement/cysteine|archive-date=1 July 2017}}</ref>

<!-- Side effects and mechanism -->

Common side effects include nausea and vomiting when taken by mouth.<ref name=AHFS2015/> The skin may occasionally become [[erythema|red]] and [[itch]]y with any route of administration.<ref name=AHFS2015/> A non-immune type of [[anaphylaxis]] may also occur.<ref name=AHFS2015/> It appears to be safe in pregnancy.<ref name=AHFS2015/> For paracetamol overdose, it works by increasing the level of [[glutathione]], an antioxidant that can neutralise the toxic breakdown products of paracetamol.<ref name=AHFS2015/> When inhaled, it acts as a [[Mucokinetics|mucolytic]] by decreasing the thickness of mucus.<ref>{{Cite journal|vauthors=Sadowska AM, Verbraecken J, Darquennes K, De Backer WA|date=December 2006|title=Role of ''N''-acetylcysteine in the management of COPD|journal=International Journal of Chronic Obstructive Pulmonary Disease|volume=1|issue=4|pages=425–434|issn=1176-9106|pmc=2707813|pmid=18044098|doi=10.2147/copd.2006.1.4.425 |doi-access=free }}</ref>

<!-- History, society and culture -->

Acetylcysteine was initially patented in 1960 and came into medical use in 1968.<ref>{{cite book | vauthors = Fischer J, Ganellin CR | title = Analogue-Based Drug Discovery | date = 2006 | publisher = Wiley-VCH | location = Weinheim | isbn = 9783527607495 | page = 544 | url = https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA544 | url-status = live | archive-url = https://web.archive.org/web/20170908143219/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA544 | archive-date = 8 September 2017 }}</ref><ref>{{Cite patent|number=US3091569A|title=Mucolytic-nu-acylated sulfhydryl compositions and process for treating animal mucus|gdate=28 May 1963|invent1=Leonard|inventor1-first=Sheffner Aaron|url=https://patents.google.com/patent/US3091569A/en}}</ref><ref>{{cite patent |country=US |number=3091569 |status=patent |title=Mucolytic-''N''-acylated sulfhydryl compositions and process for treating animal mucus |pubdate=28 May 1963 |gdate=28 May 1963 |fdate=26 August 1960 |pridate=26 August 1960 |invent1=Aaron Leonard Sheffner |assign1=Mead Johnson & Co |url=https://worldwide.espacenet.com/publicationDetails/biblio?II=2&ND=3&adjacent=true&locale=en_EP&FT=D&date=19630528&CC=US&NR=3091569A&KC=A}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | title = World Health Organization Model List of Essential Medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref>{{cite book | vauthors = Baker E | title = Top 100 Drugs: Clinical pharmacology and practical prescribing | date = 2014 | publisher = Elsevier Health Sciences | isbn = 9780702055157 | entry = Acetylcysteine | url = https://books.google.com/books?id=oeYjAwAAQBAJ&pg=PT44 | url-status = live | archive-url = https://web.archive.org/web/20170908143223/https://books.google.com/books?id=oeYjAwAAQBAJ&pg=PT44 | archive-date = 8 September 2017 }}</ref>

<!-- Storage -->

The sulfur-containing amino acids [[cysteine]] and [[methionine]] are more easily oxidized than the other amino acids.<ref>{{cite journal |vauthors=Bin P, Huang R, Zhou X |title=Oxidation Resistance of the Sulfur Amino Acids: Methionine and Cysteine. |journal=BioMed Research International |date=2017 |volume=2017 |pages=9584932 |doi=10.1155/2017/9584932 |pmid=29445748 |pmc=5763110| doi-access = free | title-link = doi }}</ref><ref name="BCLee">{{cite journal |vauthors=Lee BC, Dikiy A, Kim HY, Gladyshev VN | title=Functions and evolution of selenoprotein methionine sulfoxide reductases | journal=Biochimica et Biophysica Acta (BBA) - General Subjects | volume=1790 | issue=11 | year=2009 | pages=1471–1477 | pmid=19406207 | pmc=3062201 | doi=10.1016/j.bbagen.2009.04.014}}</ref>

== Uses ==

=== Medical uses ===

====Paracetamol overdose====

Intravenous and oral formulations of acetylcysteine are available for the treatment of [[paracetamol]] (acetaminophen) overdose.<ref name="Green et al">{{cite journal | vauthors = Green JL, Heard KJ, Reynolds KM, Albert D | title = Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis | journal = The Western Journal of Emergency Medicine | volume = 14 | issue = 3 | pages = 218–226 | date = May 2013 | pmid = 23687539 | pmc = 3656701 | doi = 10.5811/westjem.2012.4.6885 }}</ref> When paracetamol is taken in large quantities, a minor metabolite called ''N''-acetyl-''p''-benzoquinone imine ([[NAPQI]]) accumulates within the body. It is normally [[Xenobiotic metabolism#Phase II – conjugation|conjugated]] by [[glutathione]], but when taken in excess, the body's glutathione reserves are not sufficient to deactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, thereby damaging [[hepatocyte|liver cells]]. This may lead to severe liver damage and even death by [[acute liver failure]].

In the treatment of paracetamol (acetaminophen) overdose, acetylcysteine acts to maintain or replenish depleted glutathione reserves in the liver and enhance non-toxic metabolism of acetaminophen.<ref name="Acetadote Package Insert">{{cite web|title=Acetadote Package Insert|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf|publisher=FDA|access-date=19 April 2014|url-status=live|archive-url=https://web.archive.org/web/20130825114200/http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf|archive-date=25 August 2013}}</ref> These actions serve to protect liver cells from NAPQI toxicity. It is most effective in preventing or lessening hepatic injury when administered within 8–10 hours after overdose.<ref name="Acetadote Package Insert"/> Research suggests that the rate of liver toxicity is approximately 3% when acetylcysteine is administered within 10 hours of overdose.<ref name="Green et al" />

Although IV and oral acetylcysteine are equally effective for this indication, oral administration is generally poorly tolerated due to the higher dosing required to overcome its low oral [[bioavailability]],<ref>{{cite journal | vauthors = Borgström L, Kågedal B, Paulsen O | title = Pharmacokinetics of ''N''-acetylcysteine in man | journal = European Journal of Clinical Pharmacology | volume = 31 | issue = 2 | pages = 217–222 | date = 1986 | pmid = 3803419 | doi = 10.1007/bf00606662 | s2cid = 41004554 }}</ref> its foul taste and odour, and a higher incidence of [[adverse drug reaction|adverse effect]]s when taken by mouth, particularly nausea and vomiting. Prior pharmacokinetic studies of acetylcysteine did not consider [[acetylation]] as a reason for the low bioavailability of acetylcysteine.<ref name="Dilger_2007">{{cite journal | vauthors = Dilger RN, Baker DH | title = Oral ''N''-acetyl-<small>L</small>-cysteine is a safe and effective precursor of cysteine | journal = Journal of Animal Science | volume = 85 | issue = 7 | pages = 1712–1718 | date = July 2007 | pmid = 17371789 | doi = 10.2527/jas.2006-835 }}</ref> Oral acetylcysteine is identical in bioavailability to cysteine precursors.<ref name = Dilger_2007/> However, 3% to 6% of people given intravenous acetylcysteine show a severe, [[anaphylaxis]]-like allergic reaction, which may include extreme breathing difficulty (due to [[bronchospasm]]), [[hypotension|a decrease in blood pressure]], rash, [[angioedema]], and sometimes also nausea and vomiting.<ref name="pmid16990628">{{cite journal | vauthors = Kanter MZ | s2cid = 9209528 | title = Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning | journal = American Journal of Health-System Pharmacy | volume = 63 | issue = 19 | pages = 1821–1827 | date = October 2006 | pmid = 16990628 | doi = 10.2146/ajhp060050 }}</ref> Repeated doses of intravenous acetylcysteine will cause these allergic reactions to progressively worsen in these people.

Several studies have found this anaphylaxis-like reaction to occur more often in people given intravenous acetylcysteine despite serum levels of paracetamol not high enough to be considered toxic.<ref name="pmid2716644">{{cite journal | vauthors = Dawson AH, Henry DA, McEwen J | title = Adverse reactions to ''N''-acetylcysteine during treatment for paracetamol poisoning | journal = The Medical Journal of Australia | volume = 150 | issue = 6 | pages = 329–331 | date = March 1989 | pmid = 2716644 | doi = 10.5694/j.1326-5377.1989.tb136496.x| s2cid = 40296724 }}</ref><ref name="pmid9624310">{{cite journal | vauthors = Bailey B, McGuigan MA | title = Management of anaphylactoid reactions to intravenous ''N''-acetylcysteine | journal = Annals of Emergency Medicine | volume = 31 | issue = 6 | pages = 710–715 | date = June 1998 | pmid = 9624310 | doi = 10.1016/S0196-0644(98)70229-X }}</ref><ref name="pmid11167669">{{cite journal | vauthors = Schmidt LE, Dalhoff K | title = Risk factors in the development of adverse reactions to ''N''-acetylcysteine in patients with paracetamol poisoning | journal = British Journal of Clinical Pharmacology | volume = 51 | issue = 1 | pages = 87–91 | date = January 2001 | pmid = 11167669 | pmc = 2014432 | doi = 10.1046/j.1365-2125.2001.01305.x }}</ref><ref name="pmid14700565">{{cite journal | vauthors = Lynch RM, Robertson R | title = Anaphylactoid reactions to intravenous ''N''-acetylcysteine: a prospective case controlled study | journal = Accident and Emergency Nursing | volume = 12 | issue = 1 | pages = 10–15 | date = January 2004 | pmid = 14700565 | doi = 10.1016/j.aaen.2003.07.001 }}</ref>

====Lungs====

Inhaled acetylcysteine has been used for [[mucolytic]] ("mucus-dissolving") therapy in addition to other therapies in respiratory conditions with excessive and/or thick mucus production. It is also used post-operatively, as a diagnostic aid, and in [[tracheotomy]] care. It may be considered ineffective in [[cystic fibrosis]].<ref>Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.</ref> A 2013 Cochrane review in cystic fibrosis found no evidence of benefit.<ref>{{cite journal|vauthors=Tam J, Nash EF, Ratjen F, Tullis E, Stephenson A|title=Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.|journal=The Cochrane Database of Systematic Reviews|date=12 July 2013|volume=2013|issue=7|pages=CD007168|pmid=23852992|doi=10.1002/14651858.CD007168.pub3|url=http://www.repository.heartofengland.nhs.uk/157/1/Nebulized%20and%20oral%20thiol%20derivatives%20for%20pulmonary%20disease%20in%20cystic%20fibrosis..pdf|pmc=8078644|access-date=16 May 2018|archive-date=27 March 2022|archive-url=https://web.archive.org/web/20220327121154/http://www.repository.uhblibrary.co.uk/id/eprint/157/1/Nebulized%20and%20oral%20thiol%20derivatives%20for%20pulmonary%20disease%20in%20cystic%20fibrosis..pdf|url-status=dead}}</ref>

Acetylcysteine is used in the treatment of [[obstructive lung disease]] as an adjuvant treatment.<ref name="pmid10743980">{{cite journal | vauthors = Grandjean EM, Berthet P, Ruffmann R, Leuenberger P | title = Efficacy of oral long-term ''N''-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials | journal = Clinical Therapeutics | volume = 22 | issue = 2 | pages = 209–21 | date = February 2000 | pmid = 10743980 | doi = 10.1016/S0149-2918(00)88479-9 }}</ref><ref name="pmid10968500">{{cite journal | vauthors = Stey C, Steurer J, Bachmann S, Medici TC, Tramèr MR | title = The effect of oral ''N''-acetylcysteine in chronic bronchitis: a quantitative systematic review | journal = The European Respiratory Journal | volume = 16 | issue = 2 | pages = 253–262 | date = August 2000 | pmid = 10968500 | doi = 10.1034/j.1399-3003.2000.16b12.x | doi-access = free | title-link = doi }}</ref><ref name="pmid11375228">{{cite journal | vauthors = Poole PJ, Black PN | title = Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review | journal = BMJ | volume = 322 | issue = 7297 | pages = 1271–1274 | date = May 2001 | pmid = 11375228 | pmc = 31920 | doi = 10.1136/bmj.322.7297.1271 }}</ref>

=== Other uses===

Acetylcysteine has been used to [[Chelation|complex]] [[palladium]], to help it dissolve in water. This helps to remove palladium from drugs or precursors synthesized by palladium-catalyzed [[coupling reaction]]s.<ref>{{cite journal | vauthors = Garrett CE, Prasad K |title=The Art of Meeting Palladium Specifications in Active Pharmaceutical Ingredients Produced by Pd-Catalyzed Reactions |journal=Advanced Synthesis & Catalysis |volume=346 |pages=889–900 |year=2004 |doi=10.1002/adsc.200404071 |issue=8|s2cid=94929244 }}</ref> ''N''-acetylcysteine can be used to protect the liver.<ref>{{citation |title=Acetylcysteine |url=https://livertox.nih.gov/Acetylcysteine.htm |website=livertox.nih.gov |pmid=31643176 |access-date=26 April 2019}}</ref>

====Microbiological use====

Acetylcysteine can be used in Petroff's method of liquefaction and decontamination of [[sputum]], in preparation for recovery of [[mycobacterium]].<ref name=Bujitels>{{cite journal | vauthors = Buijtels PC, Petit PL | title = Comparison of NaOH–''N''-acetyl cysteine and sulfuric acid decontamination methods for recovery of mycobacteria from clinical specimens | journal = Journal of Microbiological Methods | volume = 62 | issue = 1 | pages = 83–88 | date = July 2005 | pmid = 15823396 | doi = 10.1016/j.mimet.2005.01.010 }}</ref> It also displays significant antiviral activity against the [[Influenzavirus A|influenza A viruses]].<ref name="pmid19732754">{{cite journal | vauthors = Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J | title = ''N''-Acetyl-<small>L</small>-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus | journal = Biochemical Pharmacology | volume = 79 | issue = 3 | pages = 413–420 | date = February 2010 | pmid = 19732754 | doi = 10.1016/j.bcp.2009.08.025 | url = https://hal.archives-ouvertes.fr/hal-00538093/file/PEER_stage2_10.1016%252Fj.bcp.2009.08.025.pdf }}</ref>

Acetylcysteine has [[bactericidal]] properties and breaks down bacterial [[biofilm]]s of clinically relevant pathogens including ''[[Pseudomonas aeruginosa]]'', ''[[Staphylococcus aureus]]'', ''[[Enterococcus faecalis]]'', ''[[Enterobacter cloacae]]'', ''[[Staphylococcus epidermidis]]'', and ''[[Klebsiella pneumoniae]]''.<ref>{{cite journal | vauthors = Aslam S, Darouiche RO | title = Role of antibiofilm-antimicrobial agents in controlling device-related infections | journal = The International Journal of Artificial Organs | volume = 34 | issue = 9 | pages = 752–758 | date = September 2011 | pmid = 22094553 | pmc = 3251652 | doi = 10.5301/ijao.5000024 }}</ref>

==Side effects==

{{redirect|SNOAC|the gene|snoaC{{!}}''sno''aC}}

The most commonly reported adverse effects for IV formulations of acetylcysteine are rash, [[urticaria]], and [[pruritus|itchiness]].<ref name="Acetadote Package Insert" />

Adverse effects for inhalational formulations of acetylcysteine include nausea, vomiting, [[stomatitis]], fever, [[rhinorrhea]], drowsiness, clamminess, chest tightness, and bronchoconstriction. Although infrequent, bronchospasm has been reported to occur unpredictably in some patients.<ref name="Mucomyst Package Insert">{{cite web|title=Mucomyst Package Insert|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d2dc24f3-3ad7-4c6c-8e9f-7202d9a146f7|access-date=20 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140421050640/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d2dc24f3-3ad7-4c6c-8e9f-7202d9a146f7|archive-date=21 April 2014}}</ref>

Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.<ref name="Mucomyst Package Insert"/>

Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the [[heart]] and [[lungs]].<ref name="Palmer_2007">{{cite journal | vauthors = Palmer LA, Doctor A, Chhabra P, Sheram ML, Laubach VE, Karlinsey MZ, Forbes MS, Macdonald T, Gaston B | title = ''S''-Nitrosothiols signal hypoxia-mimetic vascular pathology | journal = The Journal of Clinical Investigation | volume = 117 | issue = 9 | pages = 2592–2601 | date = September 2007 | pmid = 17786245 | pmc = 1952618 | doi = 10.1172/JCI29444 }}</ref> They found that acetylcysteine was [[drug metabolism|metabolized]] to ''S''-nitroso-''N''-acetylcysteine ('''{{vanchor|SNOAC}}'''), which increased [[blood pressure]] in the lungs and [[right ventricle]] of the heart ([[pulmonary artery hypertension]]) in [[mice]] treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic [[hypoxia (medical)|hypoxia]]). The authors also found that SNOAC induced a hypoxia-like response in the [[gene expression|expression]] of several important [[gene]]s both ''[[in vitro]]'' and ''[[in vivo]]''.

The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated. The dose used by Palmer and colleagues was dramatically higher than that used in humans, the equivalent of about 20 grams per day.<ref name="Palmer_2007"/> In humans, a much lower dosages (600&nbsp;mg per day) have been observed to counteract some age-related decline in the [[hypoxic ventilatory response]] as tested by inducing prolonged [[hypoxia (medical)|hypoxia]].<ref name="pmid11861267">{{cite journal | vauthors = Hildebrandt W, Alexander S, Bärtsch P, Dröge W | s2cid = 24375953 | title = Effect of ''N''-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O₂ chemosensitivity | journal = Blood | volume = 99 | issue = 5 | pages = 1552–5 | date = March 2002 | pmid = 11861267 | doi = 10.1182/blood.V99.5.1552 | doi-access = free | title-link = doi }}</ref>

Although ''N''-acetylcysteine prevented liver damage in mice when taken before alcohol, when taken four hours after alcohol it made liver damage worse in a dose-dependent fashion.<ref name="Wang_2006">{{cite journal | vauthors = Wang AL, Wang JP, Wang H, Chen YH, Zhao L, Wang LS, Wei W, Xu DX | title = A dual effect of ''N''-acetylcysteine on acute ethanol-induced liver damage in mice | journal = Hepatology Research | volume = 34 | issue = 3 | pages = 199–206 | date = March 2006 | pmid = 16439183 | doi = 10.1016/j.hepres.2005.12.005 }}</ref>

==Pharmacology==

===Pharmacodynamics===

Acetylcysteine serves as a [[prodrug]] to [[L-cysteine|<small>L</small>-cysteine]], a precursor to the biologic antioxidant [[glutathione]]. Hence administration of acetylcysteine replenishes glutathione stores.<ref name=TGA>{{cite web|title=Product Information: Aceradote® Concentrated Injection|work=TGA eBusiness Services|publisher=Phebra Pty Ltd|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03960-3|format=PDF|date=16 January 2013|access-date=8 November 2013|url-status=live|archive-url=https://web.archive.org/web/20170908143219/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03960-3|archive-date=8 September 2017}}</ref>

* Glutathione, along with [[oxidized glutathione]] (GSSG) and [[S-nitrosoglutathione|''S''-nitrosoglutathione]] (GSNO), have been found to bind to the [[glutamate]] recognition site of the [[NMDA receptor|NMDA]] and [[AMPA receptor]]s (via their γ-glutamyl moieties), and may be [[endogenous]] [[neuromodulator]]s.<ref name="SteulletNeijt2006">{{cite journal|vauthors=Steullet P, Neijt HC, Cuénod M, Do KQ|title=Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: Relevance to schizophrenia|journal=Neuroscience|volume=137|issue=3|year=2006|pages=807–819|issn=0306-4522|doi=10.1016/j.neuroscience.2005.10.014|pmid=16330153|s2cid=1417873}}</ref><ref name="VargaJenei1997">{{cite journal|vauthors=Varga V, Jenei Z, Janáky R, Saransaari P, Oja SS|journal=Neurochemical Research|title=Glutathione Is an Endogenous Ligand of Rat Brain ''N''-Methyl-<small>D</small>-Aspartate (NMDA) and 2-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate (AMPA) Receptors|volume=22|issue=9|year=1997|pages=1165–1171|issn=0364-3190|doi=10.1023/A:1027377605054|pmid=9251108|s2cid=24024090}}</ref> At [[millimolar]] concentrations, they may also modulate the redox state of the NMDA receptor complex.<ref name="VargaJenei1997" /> In addition, glutathione has been found to bind to and activate [[ionotropic receptor]]s that are different from any other [[excitatory amino acid receptor]], and which may constitute ''glutathione receptors'', potentially making it a [[neurotransmitter]].<ref name="Oja2000">{{cite journal|vauthors=Oja SS|title=Modulation of glutamate receptor functions by glutathione|journal=Neurochemistry International|volume=37|issue=2–3|year=2000|pages=299–306|issn=0197-0186|doi=10.1016/S0197-0186(00)00031-0|pmid=10812215|s2cid=44380765}}</ref> As such, since ''N''-acetylcysteine is a prodrug of glutathione, it may modulate all of the aforementioned receptors as well.

* Glutathione also modulates the [[NMDA receptor]] by acting at the redox site.<ref name="Berk et al 2013"/><ref name="DOI2008">{{cite journal | vauthors = Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O, Bovet P, Bush AI, Conus P, Copolov D, Fornari E, Meuli R, Solida A, Vianin P, Cuénod M, Buclin T, Do KQ | title = Glutathione precursor, ''N''-acetyl-cysteine, improves mismatch negativity in schizophrenia patients | journal = Neuropsychopharmacology | volume = 33 | issue = 9 | pages = 2187–2199 | date = August 2008 | pmid = 18004285 | doi = 10.1038/sj.npp.1301624 | doi-access = free | title-link = doi | hdl = 10536/DRO/DU:30071388 | hdl-access = free }}</ref>

L-cysteine also serves as a precursor to [[cystine]], which in turn serves as a substrate for the [[SLC7A11|cystine-glutamate antiporter]] on [[astrocytes]]; hence there is increasing glutamate release into the extracellular space. This glutamate in turn acts on [[metabotropic glutamate receptor|mGluR_2/3]] receptors, and at higher doses of acetylcysteine, [[metabotropic glutamate receptor 5|mGluR₅]].<ref name="BM2008">{{cite journal | vauthors = Dodd S, Dean O, Copolov DL, Malhi GS, Berk M | title = ''N''-Acetylcysteine for antioxidant therapy: pharmacology and clinical utility | journal = Expert Opinion on Biological Therapy | volume = 8 | issue = 12 | pages = 1955–1962 | date = December 2008 | pmid = 18990082 | doi = 10.1517/14728220802517901 | s2cid = 74736842 }}</ref><ref name="NAc2012">{{cite journal | vauthors = Kupchik YM, Moussawi K, Tang XC, Wang X, Kalivas BC, Kolokithas R, Ogburn KB, Kalivas PW | title = The effect of ''N''-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine | journal = Biological Psychiatry | volume = 71 | issue = 11 | pages = 978–986 | date = June 2012 | pmid = 22137594 | pmc = 3340445 | doi = 10.1016/j.biopsych.2011.10.024 }}</ref> Acetylcysteine may have other biological functions in the brain, such as the modulation of dopamine release and the reduction in inflammatory cytokine formation possibly via inhibiting [[NF-κB]] and modulating cytokine synthesis.<ref name="Berk et al 2013" /> These properties, along with the reduction of oxidative stress and the re‐establishment of glutamatergic balance, would lead to an increase in growth factors, such as brain‐derived neurotrophic factor ([[BDNF]]), and the regulation of neuronal cell death through B‐cell lymphoma 2 expression ([[Bcl-2|BLC-2]]).<ref name="Dean et al 2011" />

===Pharmacokinetics===

Acetylcysteine is extensively liver metabolized, CYP450 minimal, urine excretion is 22–30% with a [[half-life]] of 5.6 hours in adults and 11 hours in newborns.

==Chemistry==

Acetylcysteine is the ''N''-[[acetyl]] derivative of the amino acid <small>L</small>-cysteine, and is a precursor in the formation of the antioxidant [[glutathione]] in the body. The [[thiol]] (sulfhydryl) group confers antioxidant effects and is able to [[Redox|reduce]] [[free radical]]s.

''N''-acetyl-<small>L</small>-cysteine is soluble in water and alcohol, and practically insoluble in chloroform and ether.<ref>{{cite web|title=''N''-Acetyl-<small>L</small>-cysteine &#124; C₅H₉NO₃S|work = PubChem |publisher=National Center for Biotechnology Information, U.S. National Library of Medicine |url=https://pubchem.ncbi.nlm.nih.gov/compound/N-Acetyl-L-cysteine#section=Chemical-and-Physical-Properties|access-date=22 July 2016|url-status=live|archive-url=https://web.archive.org/web/20160816171151/https://pubchem.ncbi.nlm.nih.gov/compound/N-Acetyl-L-cysteine#section=Chemical-and-Physical-Properties|archive-date=16 August 2016}}</ref>

It is a white to white with light yellow cast powder, and has a [[pKa|p''K''_a]] of 9.5 at 30&nbsp;°C.<ref name=sial>{{cite web|title=''N''-Acetyl-<small>L</small>-cysteine Product Information |url=https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma-Aldrich/Product_Information_Sheet/a7250pis.pdf |website=Sigma |publisher=Sigma-Aldrich |access-date=9 November 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140611120709/http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma-Aldrich/Product_Information_Sheet/a7250pis.pdf |archive-date=11 June 2014 }}</ref>

==Society and culture==

Acetylcysteine was first studied as a drug in 1963. Amazon removed acetylcysteine for sale in the US in 2021, due to claims by the FDA of it being classified as a drug rather than a supplement.<ref>{{cite news | vauthors = Long J |date=2021-05-06 |title=Amazon confirms plans on removing NAC supplements |url=https://www.naturalproductsinsider.com/regulatory/amazon-confirms-plans-removing-nac-supplements |access-date=2023-09-21}}</ref><ref>{{cite news | vauthors = Long J | date = 22 April 2021 | work = Natural Products Inside |url= https://www.naturalproductsinsider.com/regulatory/amazon-reportedly-removes-nac-containing-dietary-supplements |title=Amazon reportedly removes NAC-containing dietary supplements}}</ref><ref>{{cite news|title=Warning Letter | work = benjaminmcevoy.com|url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/benjaminmcevoycom-607149-05142020 | publisher = U.S. Food and Drug Administration }}</ref><ref>{{cite news|title=FDA Sends Warning Letters to Seven Companies Illegally Selling Hangover Products |url= https://www.fda.gov/food/cfsan-constituent-updates/fda-sends-warning-letters-seven-companies-illegally-selling-hangover-products}}</ref> In April 2022, the FDA released draft guidance on FDA's policy regarding products labeled as dietary supplements that contain ''N''-acetyl-<small>L</small>-cysteine.<ref>{{cite news|title=FDA Releases Draft Guidance on Enforcement Discretion for Certain NAC Products|url=https://www.fda.gov/food/cfsan-constituent-updates/fda-releases-draft-guidance-enforcement-discretion-certain-nac-products}}</ref> Amazon subsequently re-listed NAC products as of August 2022.<ref>{{cite web | vauthors = Long J |title=Amazon resumes sales of NAC supplements |url=https://www.naturalproductsinsider.com/regulatory/amazon-resumes-sales-nac-supplements |website=Natural Products Insider |access-date=11 January 2023 |date=25 August 2022}}</ref>

==Research==

While many [[antioxidant]]s have been researched to treat a large number of diseases by reducing the negative effect of [[oxidative stress]], acetylcysteine is one of the few that has yielded promising results, and is currently already approved for the treatment of paracetamol overdose.<ref name=":0">{{Cite journal|vauthors=Head SI|date=29 October 2017|title=Antioxidant therapy in a mouse model of Duchenne muscular dystrophy: some promising results but with a weighty caveat|journal=The Journal of Physiology|volume=595|issue=23|pages=7015|doi=10.1113/jp275232|issn=0022-3751|pmc=5709324|pmid=29034480}}</ref>

* In mouse [[Mdx mouse|mdx]] models of [[Duchenne's muscular dystrophy]], treatment with 1–2% acetylcysteine in drinking water significantly reduces muscle damage and improves strength.<ref name=":0" />

* It is being studied in conditions such as [[autism]], where cysteine and related sulfur amino acids may be depleted due to multifactorial dysfunction of methylation pathways involved in [[methionine]] catabolism.<ref>{{cite journal | vauthors = Gu F, Chauhan V, Chauhan A | s2cid = 25333289 | title = Glutathione redox imbalance in brain disorders | journal = Current Opinion in Clinical Nutrition and Metabolic Care | volume = 18 | issue = 1 | pages = 89–95 | date = January 2015 | pmid = 25405315 | doi = 10.1097/MCO.0000000000000134 }}</ref>

* Animal studies have also demonstrated its efficacy in reducing the damage associated with moderate traumatic brain or spinal injury, and also ischaemia-induced brain injury. In particular, it has been demonstrated to reduce neuronal losses and to improve cognitive and neurological outcomes associated with these traumatic events.<ref name="ReferenceA" />

* It has been suggested that acetylcysteine may help people with [[aspirin-exacerbated respiratory disease]] by increasing levels of glutathione allowing faster breakdown of [[salicylate]]s, although there is no evidence that it is of benefit.<ref name="pmid12653791">{{cite journal | vauthors = Bachert C, Hörmann K, Mösges R, Rasp G, Riechelmann H, Müller R, Luckhaupt H, Stuck BA, Rudack C | title = An update on the diagnosis and treatment of sinusitis and nasal polyposis | journal = Allergy | volume = 58 | issue = 3 | pages = 176–191 | date = March 2003 | pmid = 12653791 | doi = 10.1034/j.1398-9995.2003.02172.x | s2cid = 35319457 | doi-access = | title-link = doi }}</ref>

* Small studies have shown acetylcysteine to be of benefit to people with [[blepharitis]].<ref name="pmid16390346">{{cite journal | vauthors = Aitio ML | title = ''N''-Acetylcysteine – passe-partout or much ado about nothing? | journal = British Journal of Clinical Pharmacology | volume = 61 | issue = 1 | pages = 5–15 | date = January 2006 | pmid = 16390346 | pmc = 1884975 | doi = 10.1111/j.1365-2125.2005.02523.x }}</ref> It has been shown to reduce ocular soreness caused by [[Sjögren's syndrome]].<ref name="pmid4433493">{{cite journal | vauthors = Williamson J, Doig WM, Forrester JV, Tham MH, Wilson T, Whaley K, Dick WC | title = Management of the dry eye in Sjogren's syndrome | journal = The British Journal of Ophthalmology | volume = 58 | issue = 9 | pages = 798–805 | date = September 1974 | pmid = 4433493 | pmc = 1215027 | doi = 10.1136/bjo.58.9.798 }}</ref>

* Research has found that acetylcysteine may have otoprotective properties and could potentially be useful for preventing [[hearing loss]] and [[tinnitus]] in some cases.<ref name="Schlee 2024">{{cite book | vauthors = Schlee W, Langguth B, Ridder DD, Vanneste S, Kleinjung T, Møller AR |title=Textbook of Tinnitus |publisher=Springer |year=2024 |edition=2nd |isbn=978-3-031-35646-9 |page=394, 620}}</ref><ref name="pmid36457967">{{cite journal |vauthors=Chang PH, Liu CW, Hung SH, Kang YN |title=Effect of N-acetyl-cysteine in prevention of noise-induced hearing loss: a systematic review and meta-analysis of randomized controlled trials |journal=Archives of Medical Science |volume=18 |issue=6 |pages=1535–1541 |date=2022 |pmid=36457967 |pmc=9710288 |doi=10.5114/aoms/109126}}</ref> A 2011 study showed that ''N''-acetylcysteine may protect the human cochlea from subclinical hearing loss caused by loud noises such as impulse noise.<ref name="pmid22122955">{{cite journal | vauthors = Lindblad AC, Rosenhall U, Olofsson A, Hagerman B | title = The efficacy of N-acetylcysteine to protect the human cochlea from subclinical hearing loss caused by impulse noise: a controlled trial | journal = Noise & Health | volume = 13 | issue = 55 | pages = 392–401 | date = November–December 2011 | pmid = 22122955 | doi = 10.4103/1463-1741.90293 | title-link = doi | doi-access = free }}</ref> In animal models, it reduced age-related hearing loss.{{citation needed|date=July 2024}}

* It has been shown effective in the treatment of [[Unverricht-Lundborg disease]] in an open trial in four patients. A marked decrease in myoclonus and some normalization of somatosensory evoked potentials with acetylcysteine treatment has been documented.<ref>{{cite journal | vauthors = Edwards MJ, Hargreaves IP, Heales SJ, Jones SJ, Ramachandran V, Bhatia KP, Sisodiya S | title = ''N''-acetylcysteine and Unverricht-Lundborg disease: variable response and possible side effects | journal = Neurology | volume = 59 | issue = 9 | pages = 1447–1449 | date = November 2002 | pmid = 12427904 | doi = 10.1212/wnl.59.9.1447 }}</ref><ref>{{EMedicine|article|1153370|Ataxia with Identified Genetic and Biochemical Defects}}</ref>

* Addiction to certain addictive drugs (including [[cocaine]], [[heroin]], [[alcohol (drug)|alcohol]], and [[nicotine]]) is correlated with a persistent reduction in the expression of [[EAAT2|excitatory amino acid transporter 2]] (EAAT2) in the [[nucleus accumbens]] (NAcc);<ref name="pmid24442756" /> the reduced expression of EAAT2 in this region is implicated in addictive drug-seeking behavior.<ref name="pmid24442756" /> In particular, the long-term dysregulation of glutamate neurotransmission in the NAcc of long-term, drug-dependent users is associated with an increase in vulnerability to [[relapse]] after re-exposure to the addictive drug or its associated [[drug cues]].<ref name="pmid24442756" /> Drugs that help to normalize the expression of EAAT2 in this region, such as ''N''-acetylcysteine, have been proposed as an [[adjunct therapy]] for the treatment of addiction to cocaine, nicotine, alcohol, and other drugs.<ref name="pmid24442756" />

* It has been tested for the reduction of hangover symptoms, though the overall results indicate very limited efficacy.<ref>{{ClinicalTrialsGov|NCT02541422|Use of NAC in Alleviation of Hangover Symptoms – Study Results}}</ref><ref>{{cite journal | vauthors = Coppersmith V, Hudgins S, Stoltzfus J, Stankewicz H | title = The use of N-acetylcysteine in the prevention of hangover: a randomized trial | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 13397 | date = June 2021 | pmid = 34183702 | doi = 10.1038/s41598-021-92676-0 | pmc = 8238992 | s2cid = 235673455 | bibcode = 2021NatSR..1113397C }}</ref>

* A double-blind placebo controlled trial of 262 patients has shown NAC treatment was well-tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed.<ref>{{cite journal |vauthors=De Flora S, Grassi C, Carati L |title=Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term ''N''-acetylcysteine treatment |journal=European Respiratory Journal |date=1 July 1997 |volume=10 |issue=7 |pages=1535–1541 |doi=10.1183/09031936.97.10071535 |pmid=9230243 | doi-access = free | title-link = doi }}</ref>

===Kidney and bladder===

N-acetylcysteine has been widely believed to prevent adverse effects of long term [[Ketamine]] on the bladder and kidneys, and there is growing body of evidence to support this.<ref>{{cite journal | vauthors = Ryu CM, Shin JH, Yu HY, Ju H, Kim S, Lim J, Heo J, Lee S, Shin DM, Choo MS | title = N-acetylcysteine prevents bladder tissue fibrosis in a lipopolysaccharide-induced cystitis rat model | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 8134 | date = May 2019 | pmid = 31148586 | pmc = 6544636 | doi = 10.1038/s41598-019-44631-3 | bibcode = 2019NatSR...9.8134R }}</ref>

Evidence for the benefit of acetylcysteine to prevent [[radiocontrast]] induced [[kidney disease]] is mixed.<ref>{{cite journal |vauthors=Pistolesi V, Regolisti G, Morabito S, Gandolfini I, Corrado S, Piotti G, Fiaccadori E |title=Contrast medium induced acute kidney injury: a narrative review. |journal=Journal of Nephrology |date=December 2018 |volume=31 |issue=6 |pages=797–812 |doi=10.1007/s40620-018-0498-y |pmid=29802583|s2cid=44128861 }}</ref>

Acetylcysteine has been used for [[cyclophosphamide]]-induced haemorrhagic [[cystitis]], although [[mesna]] is generally preferred due to the ability of acetylcysteine to diminish the effectiveness of cyclophosphamide.<ref>{{cite web |title=Hemorrhagic Cystitis Treatment & Management: Approach Considerations, Clot Evacuation, Bladder Irrigation Agents |url=https://emedicine.medscape.com/article/2056130-treatment#d12 |access-date=18 December 2019 |date=5 December 2019}}</ref>

===Psychiatry===

Acetylcysteine has been studied for major psychiatric disorders,<ref name="repurposed2021">{{cite journal | vauthors = Bartoli F, Cavaleri D, Bachi B, Moretti F, Riboldi I, Crocamo C, Carrà G | title = Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials | journal = Journal of Psychiatric Research | date = September 2021 | volume = 143 | pages = 230–238 | doi = 10.1016/j.jpsychires.2021.09.018| pmid = 34509090 | s2cid = 237485915 }}</ref><ref name="Dean et al 2011"/><ref name="Berk et al 2013"/><ref name="ReferenceA">{{cite journal | vauthors = Bavarsad Shahripour R, Harrigan MR, Alexandrov AV | title = ''N''-Acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities | journal = Brain and Behavior | volume = 4 | issue = 2 | pages = 108–122 | date = March 2014 | pmid = 24683506 | pmc = 3967529 | doi = 10.1002/brb3.208 }}</ref> including [[bipolar disorder]],<ref name="repurposed2021" /> [[major depressive disorder]], and [[schizophrenia]].<ref name="Dean et al 2011">{{cite journal | vauthors = Dean O, Giorlando F, Berk M | title = ''N''-Acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action | journal = Journal of Psychiatry & Neuroscience | volume = 36 | issue = 2 | pages = 78–86 | date = March 2011 | pmid = 21118657 | pmc = 3044191 | doi = 10.1503/jpn.100057 }}</ref><ref name="Berk et al 2013">{{cite journal | vauthors = Berk M, Malhi GS, Gray LJ, Dean OM | title = The promise of ''N''-acetylcysteine in neuropsychiatry | journal = Trends in Pharmacological Sciences | volume = 34 | issue = 3 | pages = 167–177 | date = March 2013 | pmid = 23369637 | doi = 10.1016/j.tips.2013.01.001 }}</ref>

Tentative evidence exists for ''N''-acetylcysteine also in the treatment of [[Alzheimer's disease]], [[autism]], [[obsessive-compulsive disorder]],<ref>{{cite journal | vauthors = Carollo M, Carollo N, Montan G | title = The promise of N-acetylcysteine in the treatment of obsessive-compulsive disorder | journal = CNS Neuroscience & Therapeutics | volume = 30 | issue = 2 | pages = e14653 | date = February 2024 | pmid = 38385640 | pmc = 10883097 | doi = 10.1111/cns.14653 }}</ref> specific [[drug addiction]]s ([[cocaine]]), drug-induced [[Peripheral neuropathy|neuropathy]], [[trichotillomania]], [[excoriation disorder]], and a certain form of epilepsy ([[progressive myoclonic epilepsy|progressive myoclonic]]).<ref name="Dean et al 2011" /><ref name="Berk et al 2013"/><ref name="May 2015 Syst Rev"/> Preliminary evidence showed efficacy in [[anxiety disorder]], [[attention deficit hyperactivity disorder]] and [[mild traumatic brain injury]] although confirmatory studies are required.<ref name="May 2015 Syst Rev">{{cite journal | vauthors = Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R | title = Clinical trials of ''N''-acetylcysteine in psychiatry and neurology: A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 55 | pages = 294–321 | date = August 2015 | pmid = 25957927 | doi = 10.1016/j.neubiorev.2015.04.015 | doi-access = free | title-link = doi }}</ref><ref name="The efficacy of adjunctive N-acetyl">{{cite journal | vauthors = Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, Kohlmann K, Hewitt K, Moss K, Allwang C, Schapkaitz I, Robbins J, Cobb H, Ng F, Dodd S, Bush AI, Malhi GS | title = The efficacy of adjunctive ''N''-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial | journal = The Journal of Clinical Psychiatry | volume = 75 | issue = 6 | pages = 628–636 | date = June 2014 | pmid = 25004186 | doi = 10.4088/JCP.13m08454 | doi-access = free | title-link = doi }}</ref><ref name="N-acetyl cysteine in the treatment">{{cite journal | vauthors = Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, Sarris J | title = ''N''-Acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review | journal = Clinical Psychopharmacology and Neuroscience | volume = 13 | issue = 1 | pages = 12–24 | date = April 2015 | pmid = 25912534 | pmc = 4423164 | doi = 10.9758/cpn.2015.13.1.12 }}</ref><ref name = BBA>{{cite journal | vauthors = Samuni Y, Goldstein S, Dean OM, Berk M | title = The chemistry and biological activities of ''N''-acetylcysteine | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1830 | issue = 8 | pages = 4117–4129 | date = August 2013 | pmid = 23618697 | doi = 10.1016/j.bbagen.2013.04.016 | hdl = 11343/43874 | s2cid = 2567773 | hdl-access = free }}</ref> Tentative evidence also supports use in [[cannabis use disorder]].<ref name="N-acetylcysteine in the treatment o">{{cite journal|vauthors=Minarini A, Ferrari S, Galletti M, Giambalvo N, Perrone D, Rioli G, Galeazzi GM |title=''N''-Acetylcysteine in the treatment of psychiatric disorders: current status and future prospects.|journal=Expert Opinion on Drug Metabolism & Toxicology|volume=13|issue=3|date=2 November 2016|pages=279–292|pmid=27766914|doi=10.1080/17425255.2017.1251580|hdl=11380/1116466|s2cid=20873065|hdl-access=free}}</ref>

It is also being studied for use as a treatment of [[body-focused repetitive behavior]].<ref name=hwang2022>{{cite journal | vauthors = Hwang AS, Campbell EH, Sartori-Valinotti JC | journal=Journal of the American Academy of Dermatology | title=Evidence of N-acetylcysteine efficacy for skin picking disorder: A retrospective cohort study | volume=87 | issue=1 | pages=148–150 | date=July 2022 | doi=10.1016/j.jaad.2021.06.874 | pmid=34224772 | s2cid=235746237 | doi-access=free }}</ref><ref name=popova2022>{{cite journal | vauthors = Popova L, Mancuso J | journal=Global Pediatric Health | title=Dramatic Improvement of Trichotillomania with 6 Months of Treatment With N-Acetylcysteine | volume=9 | pages=2333794X221086576 | year=2022 | doi=10.1177/2333794X221086576 | pmid=35647220 | pmc=9133858 }}</ref>

====Addiction====

Evidence to date does not support the efficacy for ''N''-acetylcysteine in treating [[addiction]]s to [[gambling addiction|gambling]], [[methamphetamine]], or [[nicotine]].<ref name="May 2015 Syst Rev" /> Based upon limited evidence, NAC appears to normalize [[glutamate]] [[neurotransmission]] in the [[nucleus accumbens]] and other brain structures, in part by [[Downregulation and upregulation|upregulating]] the expression of [[SLC1A2|excitatory amino acid transporter 2]] (EAAT2), {{aka}} glutamate transporter 1 (GLT1), in individuals with addiction.<ref name="pmid24442756">{{cite journal | vauthors = McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM | title = Potential role of ''N''-acetylcysteine in the management of substance use disorders | journal = CNS Drugs | volume = 28 | issue = 2 | pages = 95–106 | year = 2014 | pmid = 24442756 | pmc = 4009342 | doi = 10.1007/s40263-014-0142-x }}</ref> While NAC has been demonstrated to modulate glutamate neurotransmission in adult humans who are addicted to [[cocaine]], NAC does not appear to modulate glutamate neurotransmission in healthy adult humans.<ref name="pmid24442756" /> NAC has been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.<ref name="Berk et al 2013"/>

====Bipolar disorder====

In [[bipolar disorder]], ''N''-acetylcysteine has been repurposed as an augmentation strategy for depressive episodes in light of the possible role of inflammation in the pathogenesis of [[mood disorders]]. Nonetheless, meta-analytic evidence shows that add-on ''N''-acetylcysteine was more effective than placebo only in reducing depression scales scores (low quality evidence), without positive effects on response and remission outcomes, limiting its possible role in clinical practice to date.<ref name="repurposed2021" /><ref>{{cite journal | vauthors = Nery FG, Li W, DelBello MP, Welge JA | title = N-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials | journal = Bipolar Disorders | volume = 23 | issue = 7 | pages = 707–714 | date = November 2021 | pmid = 33354859 | doi = 10.1111/bdi.13039 | s2cid = 229692736 }}</ref>

=== COVID-19 ===

Acetylcysteine is being considered as a possible treatment for [[COVID-19]].<ref>{{cite journal | vauthors = Wong KK, Lee SW, Kua KP | title=''N''-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence | journal = Journal of Inflammation Research | volume = 14 | issue = | pages = 2993–3013 | year = 2021 | pmid = 34262324 | pmc = 8274825 | doi=10.2147/JIR.S306849 | doi-access = free }}</ref><ref>{{cite journal|title=''N''-Acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study |year=2021 |pmid=34182881 |vauthors=Assimakopoulos SF, Aretha D, Komninos D, Dimitropoulou D, Lagadinou M, Leonidou L, Oikonomou I, Mouzaki A, Marangos M |journal=Infectious Diseases (London, England) |volume=53 |issue=11 |pages=847–854 |doi=10.1080/23744235.2021.1945675 |s2cid=235673520 }}</ref><ref>{{cite journal|title=Therapeutic potential of ''N''-acetyl cysteine during COVID-19 epoch |year=2022 |pmid=35433335 |vauthors=Kapur A, Sharma M, Sageena G |journal=World Journal of Virology |volume=11 |issue=2 |pages=104–106 |doi=10.5501/wjv.v11.i2.104 |pmc=8966593 |doi-access=free }}</ref>

A combination of [[guanfacine]] and N-acetylcysteine has been found to lift the "brain fog" of eight patients with [[long COVID]], according to researchers.<ref>{{cite journal | vauthors = Fesharaki-Zadeh A, Lowe N, Arnstien A | title = Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19" | journal = Neuroimmunology Reports | volume= 3 | issue = 3 | date = 2022 | page = 100154 | doi = 10.1016/j.nerep.2022.100154 | doi-access = free }}</ref>

A combination of [[glycine]] and N-acetylcysteine is suspected to have potential to safely replenish depleted [[glutathione]] levels in COVID-19 patients.<ref>{{cite journal | vauthors = Kumar P, Osahon O, Vides DB, Hanania N, Minard CG, Sekhar RV | title = Severe Glutathione Deficiency, Oxidative Stress and Oxidant Damage in Adults Hospitalized with COVID-19: Implications for GlyNAC (Glycine and ''N''-Acetylcysteine) Supplementation | journal = Antioxidants | volume = 11 | issue = 1 | pages = 50 | date = December 2021 | pmid = 35052554 | pmc = 8773164 | doi = 10.3390/antiox11010050 | doi-access = free }}</ref>

== References ==

{{Reflist}}

{{Glutamatergics}}

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[[Category:Acetamides]]

[[Category:Alpha-Amino acids]]

[[Category:Antidotes]]

[[Category:Antioxidants]]

[[Category:Excitatory amino acid receptor ligands]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Thiols]]

[[Category:Treatment of obsessive–compulsive disorder]]

[[Category:World Health Organization essential medicines]]

[[Category:Sulfur compounds]]

[[Category:Ophthalmology drugs]]