|Systematic (IUPAC) name|
|Trade names||Acetadote, Fluimucil, Mucomyst, Parvolex|
|By mouth, injection, inhalation|
|Protein binding||50 to 83%|
|Biological half-life||5.6 hours|
|Excretion||Renal (30%), faecal (3%)|
|ATC code||R05CB01 (WHO) S01XA08 (WHO) V03AB23 (WHO)|
|Specific rotation||+5 ° (c = 3% in water)|
|Melting point||109 to 110 °C (228 to 230 °F) |
|(what is this?)|
Acetylcysteine, also known as N-acetylcysteine or N-acetyl-L-cysteine (NAC), is a medication used to treat paracetamol (acetaminophen) overdose and to loosen thick mucus such as in cystic fibrosis or chronic obstructive pulmonary disease. It is available by intravenous, by mouth, or inhaled as a mist.
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. It works by increasing glutathione levels and binding with the toxic breakdown products of paracetamol.
Acetylcysteine was initially patented in 1960 and licensed for use in 1968. It is on the World Health Organization's List of Essential Medicines, most important medication needed in a basic health system. It is available as a generic medication and is not very expensive.
- 1 Uses
- 2 Adverse effects
- 3 Pharmacology
- 4 Chemistry
- 5 Dosage forms
- 6 Research
- 7 References
- 8 External links
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 inactivate 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 both IV and oral acetylcysteine are equally effective for this indication, oral administration is poorly tolerated because high oral doses are required due to low oral bioavailability, because of its very unpleasant taste and odour, and because of adverse effects, 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. In some countries, a specific intravenous formulation does not exist to treat paracetamol overdose. In these cases, the formulation used for inhalation may be used intravenously.
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.
Oral acetylcysteine is used for the prevention of radiocontrast-induced nephropathy (a form of acute kidney failure). Some studies show that prior administration of acetylcysteine decreases radiocontrast nephropathy, whereas others do not. It has been concluded that
- "Intravenous and oral N-acetylcysteine may prevent contrast-medium–induced nephropathy with a dose-dependent effect in patients treated with primary angioplasty and may improve hospital outcome."
- "Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost"
A clinical trial from 2010, however, found that acetylcysteine is ineffective for the prevention of contrast-induced nephropathy. This trial, involving 2,308 patients, found that acetylcysteine was no better than a placebo; whether acetylcysteine or the placebo was used, the incidence of nephropathy was the same — 13%.
Despite the conflicting research outcomes, the 2012 Kidney Disease: Improving Global Outcomes Guidelines suggest the use of oral acetylcysteine for the prevention of contrast-induced nephropathy in high-risk individuals, given its potential for benefit, low likelihood of adverse effects, and low cost.
Acetylcysteine has been used for cyclophosphamide-induced hemorrhagic cystitis, although mesna is generally preferred due to the ability of acetylcysteine to diminish the effectiveness of cyclophosphamide.
Obstructive lung disease
N-acetylcysteine has been successfully tried as a treatment for a number of psychiatric disorders. A systematic review from 2015, and several earlier medical reviews, indicated that there is favorable evidence for N-acetylcysteine efficacy in the treatment of autism, Alzheimer's disease, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, specific drug addictions (cocaine and cannabis), and a certain form of epilepsy (progressive myoclonic). Evidence to date does not support the efficacy for N-acetylcysteine in treating addictions to gambling, methamphetamine, or nicotine, although pilot controlled data are encouraging.
Acetylcysteine has also been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.
Acetylcysteine can be used in Petroff's method i.e. liquefaction and decontamination of sputum, in preparation for recovery of mycobacterium. It also displays significant antiviral activity against the influenza A viruses.
Acetylcysteine has bactericidal properties and breaks down bacterial biofilms of clinically relevant pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, Enterobacter cloacae, Staphylococcus epidermidis and Klebsiella pneumoniae.
Acetylcysteine is sold as a dietary supplement commonly claiming antioxidant and liver protecting effects.
The most commonly reported adverse effects for IV formulations of acetylcysteine are rash, urticaria, and pruritis. 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. Through 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.
Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry. However, clinical trials have reported inconsistent results. High levels of ROS or prolonged stress upregulates p53 and provokes a pro-oxidant response to further increase ROS, which subsequently elicits the p53-dependent apoptotic processes to eliminate damaged cells. Thus, antioxidants can accelerate tumor growth by disrupting the ROS-p53 axis apoptosis, and autophagy, processes. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production. It is not clear what dose(s) induced these effects. Additionally, it is important to reiterate that NAC does not cause cancer, it counteracts ROS accumulation caused by p53 and down-regulates p53, which in turn prevents p53-induced apoptosis and promotes autophagy. in all cells; it is a dose dependent response, and the ability to manipulate cellular apoptosis and autophagy has many therapeutic benefits.
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 4 hours after alcohol it actually 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.
Extensively liver metabolized; CYP450 minimal. Urine excretion 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.
- It is being studied in conditions, such as autism, where cysteine and related sulfur amino acids may be depleted.
- Acetylcysteine in a double-blind placebo-controlled trial appears to reduce the effects of blast induced mild traumatic brain and neurological injury in soldiers. Animal studies have also demonstrated its efficacy in reducing the damage associated with moderate traumatic brain or spinal injury, and also ischemia-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, though there is no evidence that it is of benefit.
- It has been shown to help women with PCOS (polycystic ovary syndrome) to reduce insulin problems and possibly improve fertility.
- Small studies have shown acetylcysteine to be of benefit to people with blepharitis. and has been shown to reduce ocular soreness caused by Sjogren's syndrome.
- It has been shown effective in the treatment of Unverricht-Lundborg disease in an open trial in 4 patients. A marked decrease in myoclonus and some normalization of somatosensory evoked potentials with acetylcysteine treatment has been documented.
- The effect of acetylcysteine in combination with glucocorticoids (combination group) for people who have severe alcoholic hepatitis was examined and showed that the combination of acetylcysteine with prednisolone decreased mortality significantly at one month compared to the prednisolone-only group (8% vs 24%, P=0.006). However, the improvement was not as significant at 3 months or 6 months (22% vs 34%, P=0.06) and (27% vs 38%, P=0.07). Factors that were associated with increased 6-month survival included younger age, shorter prothrombin time, lower levels of bilirubin in baseline studies, and decrease in bilirubin on day 14, all (P<0.001). Death due to hepatorenal syndrome occurred less frequently for the combination group at 6 months (9% vs 22%, P=0.02) and infections were also less frequent in the combination group as well (P=0.001). Six-month survival, the primary outcome, was not improved in conclusion.
- Acetylcysteine has been hypothesized to be beneficial in Parkinson's disease. It is currently undergoing clinical trials.
- "L-Cysteine, N-acetyl- - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 25 March 2005. Identification. Retrieved 9 January 2012.
- Stockley RA (2008). Chronic Obstructive Pulmonary Disease a Practical Guide to Management. Chichester: John Wiley & Sons. p. 750. ISBN 9780470755280.
- "Acetylcysteine". The American Society of Health-System Pharmacists. Retrieved Aug 22, 2015.
- "ACETADOTE (acetylcysteine) injection, solution [Cumberland Pharmaceuticals Inc.]". DailyMed. Cumberland Pharmaceuticals Inc. June 2013. Retrieved 8 November 2013.
- "N-ACETYL-L-CYSTEINE Product Information" (PDF). Sigma. Sigma-aldrich. Retrieved 9 November 2014.
- Fischer J, Ganellin CR (2006). Analogue-Based Drug Discovery. Weinheim: Wiley-VCH. p. 544. ISBN 9783527607495.
- "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- Baker E (2014). Top 100 drugs : clinical pharmacology and practical prescribing. p. Acetylcysteine. ISBN 9780702055157.
- 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. 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 (Jul 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 (Oct 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.
- Dawson AH, Henry DA, McEwen J (Mar 1989). "Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning". The Medical Journal of Australia 150 (6): 329–31. PMID 2716644.
- Bailey B, McGuigan MA (Jun 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 (Jan 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 (Jan 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.". The Cochrane database of systematic reviews (7): CD007168. PMID 23852992.
- Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W (Jul 2000). "Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine". The New England Journal of Medicine 343 (3): 180–4. doi:10.1056/NEJM200007203430304. PMID 10900277.
- Hoffmann U, Fischereder M, Krüger B, Drobnik W, Krämer BK (Feb 2004). "The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable". Journal of the American Society of Nephrology 15 (2): 407–10. doi:10.1097/01.ASN.0000106780.14856.55. PMID 14747387.
- Miner SE, Dzavik V, Nguyen-Ho P, Richardson R, Mitchell J, Atchison D, Seidelin P, Daly P, Ross J, McLaughlin PR, Ing D, Lewycky P, Barolet A, Schwartz L (Oct 2004). "N-acetylcysteine reduces contrast-associated nephropathy but not clinical events during long-term follow-up". American Heart Journal 148 (4): 690–5. doi:10.1016/j.ahj.2004.05.015. PMID 15459602.
- Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL (Jun 2006). "N-acetylcysteine and contrast-induced nephropathy in primary angioplasty". The New England Journal of Medicine 354 (26): 2773–82. doi:10.1056/NEJMoa054209. PMID 16807414.
- Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, Fan K, Lee CH, Lam WF (Feb 2003). "Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial". JAMA 289 (5): 553–8. doi:10.1001/jama.289.5.553. PMID 12578487.
- "Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT)". Circulation 124 (11): 1250–9. Sep 2011. doi:10.1161/CIRCULATIONAHA.111.038943. PMID 21859972.
- Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. "KDIGO Clinical Practice Guideline for Acute Kidney Injury" (PDF). Retrieved 19 April 2014.
- Palma PC, Villaça Júnior CJ, Netto Júnior NR (1986). "N-acetylcysteine in the prevention of cyclophosphamide induced haemorrhagic cystitis". International Surgery 71 (1): 36–7. PMID 3522468.
- Hemorrhagic Cystitis~treatment at eMedicine
- Grandjean EM, Berthet P, Ruffmann R, Leuenberger P (Feb 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 (Aug 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.
- Dean O, Giorlando F, Berk M (Mar 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.
- Berk M, Malhi GS, Gray LJ, Dean OM (Mar 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.
- Bavarsad Shahripour R, Harrigan MR, Alexandrov AV (Mar 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.
- Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R (Aug 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.
- 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 (Jun 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 (Apr 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 (Aug 2013). "The chemistry and biological activities of N-acetylcysteine". Biochimica et Biophysica Acta 1830 (8): 4117–29. doi:10.1016/j.bbagen.2013.04.016. PMID 23618697.
- "N-Acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake". Biological Psychiatry. doi:10.1016/j.biopsych.2015.09.019.
- Buijtels PC, Petit PL (Jul 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.
- Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J (Feb 2010). "N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus". Biochemical Pharmacology 79 (3): 413–20. doi:10.1016/j.bcp.2009.08.025. PMID 19732754.
- Aslam S, Darouiche RO (Sep 2011). "Role of antibiofilm-antimicrobial agents in controlling device-related infections". The International Journal of Artificial Organs 34 (9): 752–8. doi:10.5301/ijao.5000024. PMC 3251652. PMID 22094553.
- 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.
- "Mucomyst Package Insert". Retrieved 20 April 2014.
- Bjelakovic G, Nikolova D, Gluud C (Sep 2013). "Antioxidant supplements to prevent mortality". JAMA 310 (11): 1178–9. doi:10.1001/jama.2013.277028. PMID 24045742.
- Chen W, Jiang T, Wang H, Tao S, Lau A, Fang D, Zhang DD (Dec 2012). "Does Nrf2 contribute to p53-mediated control of cell survival and death?". Antioxidants & Redox Signaling 17 (12): 1670–5. doi:10.1089/ars.2012.4674. PMC 3474188. PMID 22559194.
- Bensaad K, Vousden KH (Dec 2005). "Savior and slayer: the two faces of p53". Nature Medicine 11 (12): 1278–9. doi:10.1038/nm1205-1278. PMID 16333263.
- Faraonio R, Vergara P, Di Marzo D, Pierantoni MG, Napolitano M, Russo T, Cimino F (Dec 2006). "p53 suppresses the Nrf2-dependent transcription of antioxidant response genes". The Journal of Biological Chemistry 281 (52): 39776–84. doi:10.1074/jbc.M605707200. PMID 17077087.
- Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MO (Jan 2014). "Antioxidants accelerate lung cancer progression in mice". Science Translational Medicine 6 (221): 221ra15. doi:10.1126/scitranslmed.3007653. PMID 24477002.
- Sablina AA, Budanov AV, Ilyinskaya GV, Agapova LS, Kravchenko JE, Chumakov PM (Dec 2005). "The antioxidant function of the p53 tumor suppressor". Nature Medicine 11 (12): 1306–13. doi:10.1038/nm1320. PMC 2637821. PMID 16286925.
- Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I (Feb 2015). "Autophagy has a key role in the pathophysiology of schizophrenia". Molecular Psychiatry 20 (1): 126–32. doi:10.1038/mp.2013.174. PMID 24365867.
- Li J, Ghiani CA, Kim JY, Liu A, Sandoval J, DeVellis J, Casaccia-Bonnefil P (Jun 2008). "Inhibition of p53 transcriptional activity: a potential target for future development of therapeutic strategies for primary demyelination". The Journal of Neuroscience 28 (24): 6118–27. doi:10.1523/JNEUROSCI.0184-08.2008. PMC 2962898. PMID 18550754.
- Laposa RR, Huang EJ, Cleaver JE (Jan 2007). "Increased apoptosis, p53 up-regulation, and cerebellar neuronal degeneration in repair-deficient Cockayne syndrome mice". Proceedings of the National Academy of Sciences of the United States of America 104 (4): 1389–94. doi:10.1073/pnas.0610619104. PMC 1783131. PMID 17229834.
- La Spada AR, Morrison RS (Jul 2005). "The power of the dark side: Huntington's disease protein and p53 form a deadly alliance". Neuron 47 (1): 1–3. doi:10.1016/j.neuron.2005.06.023. PMID 15996541.
- Palmer LA, Doctor A, Chhabra P, Sheram ML, Laubach VE, Karlinsey MZ, Forbes MS, Macdonald T, Gaston B (Sep 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.
- "The Overlooked Compound That Saves Lives". Retrieved 8 July 2013. Julius Goepp, MD. Published in Life Extension, May 2010, quote: ". . . the doses they used correspond to a human dose of about 20 grams (20,000 mg) per day."
- Hildebrandt W, Alexander S, Bärtsch P, Dröge W (Mar 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.
- Wang AL, Wang JP, Wang H, Chen YH, Zhao L, Wang LS, Wei W, Xu DX (Mar 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. 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.
- Varga, V.; Jenei, Zs.; Janáky, R.; Saransaari, P.; Oja, S. S. (1997). Neurochemical Research 22 (9): 1165–1171. doi:10.1023/A:1027377605054. ISSN 0364-3190. Missing or empty
- 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.
- 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 (Aug 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 (Dec 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 (Jun 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". Retrieved 22 July 2016.
- "N-ACETYL-L-CYSTEINE Product Information" (PDF). Sigma. Sigma-aldrich. Retrieved 9 November 2014.
- Gu F, Chauhan V, Chauhan A (Jan 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.
- Hoffer ME, Balaban C, Slade MD, Tsao JW, Hoffer B (2013). "Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetyl cysteine: a double-blind, placebo controlled study". PLOS ONE 8 (1): e54163. doi:10.1371/journal.pone.0054163. PMC 3553161. PMID 23372680.
- Bachert C, Hörmann K, Mösges R, Rasp G, Riechelmann H, Müller R, Luckhaupt H, Stuck BA, Rudack C (Mar 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.
- Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A (Jun 2002). "N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome". Fertility and Sterility 77 (6): 1128–35. doi:10.1016/S0015-0282(02)03133-3. PMID 12057717.
- Aitio ML (Jan 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 (Sep 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 (Nov 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
- Nguyen-Khac E, Thevenot T, Piquet MA, Benferhat S, Goria O, Chatelain D, Tramier B, Dewaele F, Ghrib S, Rudler M, Carbonell N, Tossou H, Bental A, Bernard-Chabert B, Dupas JL (Nov 2011). "Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis". The New England Journal of Medicine 365 (19): 1781–9. doi:10.1056/NEJMoa1101214. PMID 22070475.
- Martínez-Banaclocha MA (Jul 2012). "N-acetyl-cysteine in the treatment of Parkinson's disease. What are we waiting for?". Medical Hypotheses 79 (1): 8–12. doi:10.1016/j.mehy.2012.03.021. PMID 22546753.
- N-Acetylcysteine for Neuroprotection in Parkinson's Disease (NAC for PD)
- Repeated-Dose Oral N-acetylcysteine for the Treatment of Parkinson's Disease