|Pronunciation||// and similar (/ -, - /-,)|
|Trade names||Acetadote, Fluimucil, Mucomyst, others|
|Other names||N-acetylcysteine; N-acetyl-L-cysteine; NALC; NAC|
|By mouth, injection, inhalation|
|Defined daily dose||1.6 g (inhalation solution) or|
0.5 g (by mouth)
|Protein binding||50 to 83%|
|Elimination half-life||5.6 hours|
|Excretion||Renal (30%), faecal (3%)|
|Chemical and physical data|
|Molar mass||163.195 g·mol−1|
|3D model (JSmol)|
|Specific rotation||+5° (c = 3% in water)|
|Melting point||109 to 110 °C (228 to 230 °F) |
Acetylcysteine, also known as N-acetylcysteine (NAC), is a medication that is used to treat paracetamol (acetaminophen) overdose, and to loosen thick mucus in individuals with cystic fibrosis or chronic obstructive pulmonary disease. It can be taken intravenously, by mouth, or inhaled as a mist. Some people use it as a dietary supplement.
Common side effects include nausea and vomiting when taken by mouth. The skin may occasionally become red and itchy with either form. A non-immune type of anaphylaxis may also occur. It appears to be safe in pregnancy. For paracetamol overdose, it works by increasing the level of glutathione, an antioxidant that can neutralise the toxic breakdown products of paracetamol. When inhaled, it acts as a mucolytic by decreasing the thickness of mucus.
Acetylcysteine was initially patented in 1960 and came into medical use in 1968. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication and is inexpensive.
Intravenous and oral formulations of acetylcysteine are available for the treatment of paracetamol (acetaminophen) overdose. When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body. It is normally 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 liver cells. This may lead to severe liver damage and even death by acute liver failure.
In the treatment of acetaminophen overdose, acetylcysteine acts to maintain or replenish depleted glutathione reserves in the liver and enhance non-toxic metabolism of acetaminophen. 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. Research suggests that the rate of liver toxicity is approximately 3% when acetylcysteine is administered within 10 hours of overdose.
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, its foul taste and odour, and a higher incidence of adverse effects 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. Oral acetylcysteine is identical in bioavailability to cysteine precursors. 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), a decrease in blood pressure, rash, angioedema, and sometimes also nausea and vomiting. 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 IV acetylcysteine despite serum levels of paracetamol not high enough to be considered toxic.
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. A 2013 Cochrane review in cystic fibrosis found no evidence of benefit.
Kidney and bladder
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.
Acetylcysteine has been used to complex palladium, to help it dissolve in water. This helps to remove palladium from drugs or precursors synthesized by palladium-catalyzed coupling reactions. N-actelylcysteine can be used to protect the liver.
- By injection
- Loading dose: 150mg/kg in 100 mL D5W over 60min
- Second (maintenance) dose: 50mg/kg in 250 mL D5W over 4hr
- Third dose: 100mg/kg in 500 mL D5W over 16hr
- By mouth
- Less preferred than IV route due to unpleasant taste and smell
- 140 mg/kg PO load
- 70 mg/kg PO q4hr x17 doses additional; dilute to 5% soln
The most commonly reported adverse effects for IV formulations of acetylcysteine are rash, urticaria, and itchiness. Up to 18% of patients have been reported to experience anaphylaxis reaction, which are defined as rash, hypotension, wheezing, and/or shortness of breath. Lower rates of anaphylactoid reactions have been reported with slower rates of infusion.
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.
Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.
Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs. They found that acetylcysteine was metabolized to S-nitroso-N-acetylcysteine (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). The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes 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. Nonetheless, positive effects on age-diminished control of respiration (the hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.
Although N-acetylcysteine prevented liver damage when taken before alcohol, when taken four hours after alcohol it made liver damage worse in a dose-dependent fashion.
– Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), have been found to bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties), and may be endogenous neuromodulators. At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex. In addition, glutathione has been found to bind to and activate ionotropic receptors that are different from any other excitatory amino acid receptor, and which may constitute glutathione receptors, potentially making it a neurotransmitter. As such, since N-acetylcysteine is a prodrug of glutathione, it may modulate all of the aforementioned receptors as well.
L-cysteine also serves as a precursor to cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of acetylcysteine, mGluR5.
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 neonates.
Acetylcysteine is the N-acetyl derivative of the amino acid L-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 reduce free radicals.
N-acetyl-L-cysteine is soluble in water and alcohol, and practically insoluble in chloroform and ether.
It is a white to white with light yellow cast powder, and has a pKa of 9.5 at 30 °C.
Acetylcysteine is available in different dosage forms for different indications:
- Solution for inhalation (Assist, Mucomyst, Mucosil) – inhaled for mucolytic therapy or ingested for nephroprotective effect (kidney protection)
- Intravenous injection (Assist, Parvolex, Acetadote) – treatment of paracetamol/acetaminophen overdose
- Oral solution – various indications.
- Effervescent tablets
- Ocular solution - for mucolytic therapy
- Tablets - sometimes in a sustained release formula sold as a nutritional supplement
The IV injection and inhalation preparations are, in general, prescription only, whereas the oral solution and the effervescent tablets are available over the counter in many countries. Acetylcysteine is available as a health supplement in the United States, typically in capsule form.
While many antioxidants 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.
- In mouse mdx models of Duchenne's muscular dystrophy, treatment with 1-2% acetylcysteine in drinking water significantly reduces muscle damage and improves strength.
- 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.
- 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.
- It has been suggested that acetylcysteine may help people with Samter's triad by increasing levels of glutathione allowing faster breakdown of salicylates, although there is no evidence that it is of benefit.
- Small studies have shown acetylcysteine to be of benefit to people with blepharitis, and it has been shown to reduce ocular soreness caused by Sjögren's syndrome.
- 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.
- Addiction to certain addictive drugs (e.g., cocaine, heroin, alcohol, and nicotine) is correlated with a persistent reduction in the expression of excitatory amino acid transporter 2 (EAAT2) in the nucleus accumbens (NAcc); the reduced expression of EAAT2 in this region is implicated in addictive drug-seeking behavior. In particular, the long-term dysregulation of glutamate neurotransmission in the NAcc of addicts is associated with an increase in vulnerability to relapse after re-exposure to the addictive drug or its associated drug cues. 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.
- It has been tested for the reduction of hangover symptoms, but one clinical trial found no significant change between those receiving the drug and placebo.
Acetylcysteine has been studied for a number of psychiatric disorders. Several reviews found tentative evidence for N-acetylcysteine in the treatment of Alzheimer's disease, autism, bipolar disorder, drug-induced neuropathy, major depressive disorder, obsessive-compulsive disorder, schizophrenia, specific drug addictions (cocaine), trichotillomania, excoriation disorder, and a certain form of epilepsy (progressive myoclonic). Preliminary evidence showed efficacy in anxiety disorder, attention deficit hyperactivity disorder and mild traumatic brain injury although confirmatory studies are required. Tentative evidence also supports use in cannabis use disorder.
Evidence to date does not support the efficacy for N-acetylcysteine in treating addictions to gambling, methamphetamine, or nicotine. Based upon limited evidence, NAC appears to normalize glutamate neurotransmission in the nucleus accumbens and other brain structures, in part by upregulating the expression of excitatory amino acid transporter 2 (EAAT2), a.k.a. glutamate transporter 1 (GLT1), in individuals with addiction. 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. NAC has been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.
- "L-Cysteine, N-acetyl- - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 25 March 2005. Identification. Archived from the original on 12 January 2014. Retrieved 9 January 2012.
- "WHOCC - ATC/DDD Index". www.whocc.no. Retrieved 22 September 2020.
- Stockley RA (2008). Chronic Obstructive Pulmonary Disease a Practical Guide to Management. Chichester: John Wiley & Sons. p. 750. ISBN 9780470755280. Archived from the original on 8 September 2017.
- "Acetylcysteine". The American Society of Health-System Pharmacists. Archived from the original on 23 September 2015. Retrieved 22 August 2015.
- "ACETADOTE (acetylcysteine) injection, solution [Cumberland Pharmaceuticals Inc.]". DailyMed. Cumberland Pharmaceuticals Inc. June 2013. Archived from the original on 13 January 2014. Retrieved 8 November 2013.
- "N-ACETYL-L-CYSTEINE Product Information" (PDF). Sigma. Sigma-aldrich. Archived from the original (PDF) on 11 June 2014. Retrieved 9 November 2014.
- Talbott, Shawn M. (2012). A Guide to Understanding Dietary Supplements. Routledge. p. 469. ISBN 9781136805707. Archived from the original on 8 September 2017.
- "Cysteine". University of Maryland Medical Center. Archived from the original on 1 July 2017. Retrieved 23 June 2017.
- Sadowska, Anna M; Verbraecken, J; Darquennes, K; De Backer, WA (December 2006). "Role of N-acetylcysteine in the management of COPD". International Journal of Chronic Obstructive Pulmonary Disease. 1 (4): 425–434. doi:10.2147/copd.2006.1.4.425. ISSN 1176-9106. PMC 2707813. PMID 18044098.
- Fischer J, Ganellin CR (2006). Analogue-Based Drug Discovery. Weinheim: Wiley-VCH. p. 544. ISBN 9783527607495. Archived from the original on 8 September 2017.
- US patent 3091569, Aaron Leonard Sheffner, "Mucolytic-nu-acylated sulfhydryl compositions and process for treating animal mucus", published 1963-05-28, issued 1963-05-28, assigned to Mead Johnson & Co
- World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- Baker E (2014). Top 100 drugs : clinical pharmacology and practical prescribing. p. Acetylcysteine. ISBN 9780702055157. Archived from the original on 8 September 2017.
- Green JL, Heard KJ, Reynolds KM, Albert D (May 2013). "Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis". The Western Journal of Emergency Medicine. 14 (3): 218–26. doi:10.5811/westjem.2012.4.6885. PMC 3656701. PMID 23687539.
- "Acetadote Package Insert" (PDF). FDA. Archived (PDF) from the original on 25 August 2013. Retrieved 19 April 2014.
- Borgström L, Kågedal B, Paulsen O (1986). "Pharmacokinetics of N-acetylcysteine in man". European Journal of Clinical Pharmacology. 31 (2): 217–22. doi:10.1007/bf00606662. PMID 3803419.
- Dilger RN, Baker DH (July 2007). "Oral N-acetyl-L-cysteine is a safe and effective precursor of cysteine". Journal of Animal Science. 85 (7): 1712–8. doi:10.2527/jas.2006-835. PMID 17371789.
- Kanter MZ (October 2006). "Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning". American Journal of Health-System Pharmacy. 63 (19): 1821–7. doi:10.2146/ajhp060050. PMID 16990628. S2CID 9209528.
- Dawson AH, Henry DA, McEwen J (March 1989). "Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning". The Medical Journal of Australia. 150 (6): 329–31. doi:10.5694/j.1326-5377.1989.tb136496.x. PMID 2716644.
- Bailey B, McGuigan MA (June 1998). "Management of anaphylactoid reactions to intravenous N-acetylcysteine". Annals of Emergency Medicine. 31 (6): 710–5. doi:10.1016/S0196-0644(98)70229-X. PMID 9624310.
- Schmidt LE, Dalhoff K (January 2001). "Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning". British Journal of Clinical Pharmacology. 51 (1): 87–91. doi:10.1046/j.1365-2125.2001.01305.x. PMC 2014432. PMID 11167669.
- Lynch RM, Robertson R (January 2004). "Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study". Accident and Emergency Nursing. 12 (1): 10–5. doi:10.1016/j.aaen.2003.07.001. PMID 14700565.
- Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
- Tam, J; Nash, EF; Ratjen, F; Tullis, E; Stephenson, A (12 July 2013). "Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis" (PDF). The Cochrane Database of Systematic Reviews (7): CD007168. doi:10.1002/14651858.CD007168.pub3. PMID 23852992.
- Grandjean EM, Berthet P, Ruffmann R, Leuenberger P (February 2000). "Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials". Clinical Therapeutics. 22 (2): 209–21. doi:10.1016/S0149-2918(00)88479-9. PMID 10743980.
- Stey C, Steurer J, Bachmann S, Medici TC, Tramèr MR (August 2000). "The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review". The European Respiratory Journal. 16 (2): 253–62. doi:10.1034/j.1399-3003.2000.16b12.x. PMID 10968500.
- Poole PJ, Black PN (May 2001). "Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review". BMJ. 322 (7297): 1271–4. doi:10.1136/bmj.322.7297.1271. PMC 31920. PMID 11375228.
- Pistolesi, V; Regolisti, G; Morabito, S; Gandolfini, I; Corrado, S; Piotti, G; Fiaccadori, E (December 2018). "Contrast medium induced acute kidney injury: a narrative review". Journal of Nephrology. 31 (6): 797–812. doi:10.1007/s40620-018-0498-y. PMID 29802583.
- "Hemorrhagic Cystitis Treatment & Management: Approach Considerations, Clot Evacuation, Bladder Irrigation Agents". 5 December 2019. Retrieved 18 December 2019.
- Garrett CE, Prasad K (2004). "The Art of Meeting Palladium Specifications in Active Pharmaceutical Ingredients Produced by Pd-Catalyzed Reactions". Advanced Synthesis & Catalysis. 346 (8): 889–900. doi:10.1002/adsc.200404071.
- "Acetylcysteine", livertox.nih.gov, retrieved 26 April 2019
- Buijtels PC, Petit PL (July 2005). "Comparison of NaOH-N-acetyl cysteine and sulfuric acid decontamination methods for recovery of mycobacteria from clinical specimens". Journal of Microbiological Methods. 62 (1): 83–8. doi:10.1016/j.mimet.2005.01.010. PMID 15823396.
- "Template:Adult NAC dosing - WikEM". www.wikem.org. Retrieved 5 August 2020.
- "Mucomyst Package Insert". Archived from the original on 21 April 2014. Retrieved 20 April 2014.
- Palmer LA, Doctor A, Chhabra P, Sheram ML, Laubach VE, Karlinsey MZ, Forbes MS, Macdonald T, Gaston B (September 2007). "S-nitrosothiols signal hypoxia-mimetic vascular pathology". The Journal of Clinical Investigation. 117 (9): 2592–601. doi:10.1172/JCI29444. PMC 1952618. PMID 17786245.
- Hildebrandt W, Alexander S, Bärtsch P, Dröge W (March 2002). "Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O(2) chemosensitivity". Blood. 99 (5): 1552–5. doi:10.1182/blood.V99.5.1552. PMID 11861267. S2CID 24375953.
- Wang AL, Wang JP, Wang H, Chen YH, Zhao L, Wang LS, Wei W, Xu DX (March 2006). "A dual effect of N-acetylcysteine on acute ethanol-induced liver damage in mice". Hepatology Research. 34 (3): 199–206. doi:10.1016/j.hepres.2005.12.005. PMID 16439183.
- "PRODUCT INFORMATION ACETADOTE® CONCENTRATED INJECTION" (PDF). TGA eBusiness Services. Phebra Pty Ltd. 16 January 2013. Archived from the original on 8 September 2017. Retrieved 8 November 2013.
- Steullet, P.; Neijt, H.C.; Cuénod, M.; Do, K.Q. (2006). "Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: Relevance to schizophrenia". Neuroscience. 137 (3): 807–819. doi:10.1016/j.neuroscience.2005.10.014. ISSN 0306-4522. PMID 16330153.
- Varga, V.; Jenei, Zs.; Janáky, R.; Saransaari, P.; Oja, S. S. (1997). "Glutathione Is an Endogenous Ligand of Rat Brain N-Methyl-D-Aspartate (NMDA) and 2-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate (AMPA) Receptors". Neurochemical Research. 22 (9): 1165–1171. doi:10.1023/A:1027377605054. ISSN 0364-3190. PMID 9251108.
- Oja, S (2000). "Modulation of glutamate receptor functions by glutathione". Neurochemistry International. 37 (2–3): 299–306. doi:10.1016/S0197-0186(00)00031-0. ISSN 0197-0186. PMID 10812215.
- Berk M, Malhi GS, Gray LJ, Dean OM (March 2013). "The promise of N-acetylcysteine in neuropsychiatry". Trends in Pharmacological Sciences. 34 (3): 167–77. doi:10.1016/j.tips.2013.01.001. PMID 23369637.
- 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 (August 2008). "Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients". Neuropsychopharmacology. 33 (9): 2187–99. doi:10.1038/sj.npp.1301624. PMID 18004285.
- Dodd S, Dean O, Copolov DL, Malhi GS, Berk M (December 2008). "N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility". Expert Opinion on Biological Therapy. 8 (12): 1955–62. doi:10.1517/14728220802517901. PMID 18990082.
- Kupchik YM, Moussawi K, Tang XC, Wang X, Kalivas BC, Kolokithas R, Ogburn KB, Kalivas PW (June 2012). "The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine". Biological Psychiatry. 71 (11): 978–86. doi:10.1016/j.biopsych.2011.10.024. PMC 3340445. PMID 22137594.
- "N-Acetyl-L-cysteine | C5H9NO3S - PubChem". Archived from the original on 16 August 2016. Retrieved 22 July 2016.
- Head, Stewart I. (29 October 2017). "Antioxidant therapy in a mouse model of Duchenne muscular dystrophy: some promising results but with a weighty caveat". The Journal of Physiology. 595 (23): 7015. doi:10.1113/jp275232. ISSN 0022-3751. PMC 5709324. PMID 29034480.
- Gu F, Chauhan V, Chauhan A (January 2015). "Glutathione redox imbalance in brain disorders". Current Opinion in Clinical Nutrition and Metabolic Care. 18 (1): 89–95. doi:10.1097/MCO.0000000000000134. PMID 25405315. S2CID 25333289.
- Bavarsad Shahripour R, Harrigan MR, Alexandrov AV (March 2014). "N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities". Brain and Behavior. 4 (2): 108–22. doi:10.1002/brb3.208. PMC 3967529. PMID 24683506.
- Bachert C, Hörmann K, Mösges R, Rasp G, Riechelmann H, Müller R, Luckhaupt H, Stuck BA, Rudack C (March 2003). "An update on the diagnosis and treatment of sinusitis and nasal polyposis". Allergy. 58 (3): 176–91. doi:10.1034/j.1398-9995.2003.02172.x. PMID 12653791.
- Aitio ML (January 2006). "N-acetylcysteine -- passe-partout or much ado about nothing?". British Journal of Clinical Pharmacology. 61 (1): 5–15. doi:10.1111/j.1365-2125.2005.02523.x. PMC 1884975. PMID 16390346.
- Williamson J, Doig WM, Forrester JV, Tham MH, Wilson T, Whaley K, Dick WC (September 1974). "Management of the dry eye in Sjogren's syndrome". The British Journal of Ophthalmology. 58 (9): 798–805. doi:10.1136/bjo.58.9.798. PMC 1215027. PMID 4433493.
- Edwards MJ, Hargreaves IP, Heales SJ, Jones SJ, Ramachandran V, Bhatia KP, Sisodiya S (November 2002). "N-acetylcysteine and Unverricht-Lundborg disease: variable response and possible side effects". Neurology. 59 (9): 1447–9. doi:10.1212/wnl.59.9.1447. PMID 12427904.
- Ataxia with Identified Genetic and Biochemical Defects at eMedicine
- McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM (2014). "Potential role of N-acetylcysteine in the management of substance use disorders". CNS Drugs. 28 (2): 95–106. doi:10.1007/s40263-014-0142-x. PMC 4009342. PMID 24442756.
- "Use of NAC in Alleviation of Hangover Symptoms - Study Results - ClinicalTrials.gov". clinicaltrials.gov.
- Dean O, Giorlando F, Berk M (March 2011). "N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action". Journal of Psychiatry & Neuroscience. 36 (2): 78–86. doi:10.1503/jpn.100057. PMC 3044191. PMID 21118657.
- Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R (August 2015). "Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review". Neuroscience and Biobehavioral Reviews. 55: 294–321. doi:10.1016/j.neubiorev.2015.04.015. PMID 25957927.
In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as nicotine addictions, anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable.
- 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 (June 2014). "The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial". The Journal of Clinical Psychiatry. 75 (6): 628–36. doi:10.4088/JCP.13m08454. PMID 25004186.
- Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, Sarris J (April 2015). "N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review". Clinical Psychopharmacology and Neuroscience. 13 (1): 12–24. doi:10.9758/cpn.2015.13.1.12. PMC 4423164. PMID 25912534.
- Samuni Y, Goldstein S, Dean OM, Berk M (August 2013). "The chemistry and biological activities of N-acetylcysteine". Biochimica et Biophysica Acta (BBA) - General Subjects. 1830 (8): 4117–29. doi:10.1016/j.bbagen.2013.04.016. hdl:11343/43874. PMID 23618697.
- Minarini, A; Ferrari, S; Galletti, M; Giambalvo, N; Perrone, D; Rioli, G; Galeazzi, GM (2 November 2016). "N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects". Expert Opinion on Drug Metabolism & Toxicology. 13 (3): 279–292. doi:10.1080/17425255.2017.1251580. PMID 27766914.