|Systematic (IUPAC) name|
|Trade names||Acetadote, Fluimucil, Mucomyst, Parvolex|
|Licence data||US Daily Med:|
|Pregnancy cat.||B2 (AU) B (US)|
|Legal status||Pharmacy Only (S2) (AU) ℞-only (US)|
|Routes||Oral, injection, inhalation|
|Excretion||Renal (22%), faecal (3%)|
|ATC code||R05 S01 V03|
|Melt. point||106 °C (223 °F)|
|Boiling point||108 °C (226 °F)|
|Solubility in water||5.1 mg/mL (20 °C)|
|(what is this?)|
Acetylcysteine rINN //, also known as N-acetylcysteine or N-acetyl-L-cysteine (abbreviated NAC), is a pharmaceutical drug and nutritional supplement used primarily as a mucolytic agent and in the management of paracetamol (acetaminophen) overdose. Other uses include sulfate repletion in conditions, such as autism, where cysteine and related sulfur amino acids may be depleted.
Acetylcysteine is a derivative of cysteine; an acetyl group that is attached to the nitrogen atom. This compound is sold as a dietary supplement commonly claiming antioxidant and liver protecting effects. It is used as a cough medicine because it breaks disulfide bonds in mucus and liquefies it, making it easier to cough up. It is also this action of breaking disulfide bonds that makes it useful in thinning the abnormally thick mucus in cystic and pulmonary fibrosis patients.
- 1 Medical uses
- 2 Adverse effects
- 3 Mechanism of action
- 4 Complexing agent
- 5 Chemistry
- 6 Dosage forms
- 7 Research
- 8 References
- 9 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, therefore damaging hepatocytes. 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 hepatocytes in the liver 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 hepatotoxicity 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 is indicated for mucolytic ("mucus-dissolving") therapy as an adjuvant in respiratory conditions with excessive and/or thick mucus production. Such conditions include emphysema, bronchitis, tuberculosis, bronchiectasis, amyloidosis, pneumonia, cystic fibrosis, chronic obstructive pulmonary disease, and pulmonary fibrosis. It is also used post-operatively, as a diagnostic aid, and in tracheotomy care. It may be considered ineffective in cystic fibrosis. However, a recent paper in the Proceedings of the National Academy of Sciences reports that high-dose oral acetylcysteine modulates inflammation in cystic fibrosis and has the potential to counter the intertwined redox and inflammatory imbalances in CF. Oral acetylcysteine may also be used as a mucolytic in less serious cases.
For this indication, acetylcysteine acts to reduce mucus viscosity by splitting disulfide bonds linking proteins present in the mucus (mucoproteins). Furthermore, with respect to its use as a mucolytic agent in patients with COPD, it is hypothesized that acetylcysteine may exert additional beneficial effects through its anti-inflammatory and antioxidant properties.
Oral acetylcysteine is used for the prevention of radiocontrast-induced nephropathy (a form of acute renal failure). Some studies show that prior administration of acetylcysteine markedly decreases radiocontrast nephropathy, whereas others appear to cast doubt on its efficacy. 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 placebo; whether acetylcysteine or 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.
Treatment of cyclophosphamide-induced hemorrhagic cystitis
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.
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.
Interstitial lung disease
Acetylcysteine is used in the treatment of interstitial lung disease to prevent disease progression. Oxidative stress and depleted stores of the antioxidant glutathione have been hypothesized to contribute to interstitial lung diseases, such as idiopathic pulmonary fibrosis. Acetylcysteine, as a precursor to the antioxidant glutathione, has been found to increase levels of glutathione in lung tissue in patients with idiopathic pulmonary fibrosis. 
Acetylcysteine has been successfully tried as a treatment for a multitude of psychiatric disorders. In particular, as a treatment for schizophrenia, bipolar disorder, trichotillomania, skin picking, autism, obsessive-compulsive disorder, drug (including nicotine, cannabis, methamphetamine, cocaine, etc.) and gambling addiction.
Acetylcysteine's ability to suppress p53-induced apoptosis and promote autophagy may be a contributing factor in its effectiveness in treating neuro-psychiatric disorders. Acetylcysteine has also been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.
Polycystic ovary syndrome
In a small prospective trial comparing acetylcysteine to metformin (which is the standard drug treatment for PCOS), both treatments resulted in a significant decrease in body mass index, hirsutism score, fasting insulin, HOMA index, free testosterone and menstrual irregularity compared with baseline values, and both treatments had equal efficacy.
Traumatic brain injury
Acetylcysteine has been shown to have efficacy in treating mild to moderate traumatic brain injury, particularly in reducing neuronal losses, and also reducing cognitive and neurological symptoms when administered promptly after injury.
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 anaphylactoid reactions, 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, and supported by some scientific studies. However, clinical trials have reported inconsistent results. Supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increased tumor progression and reduced survival in mouse models of B-RAF and K-RAS induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. 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 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.
Mechanism of action
Acetylcysteine serves as a prodrug to L-cysteine which is a precursor to the biologic antioxidant, glutathione and hence administration of acetylcysteine replenishes glutathione stores. 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. Glutathione also modulates the NMDA receptor by acting at the redox site. Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB and modulating cytokine synthesis. It may also facilitate dopamine release in certain brain areas.
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.
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 (to protect the kidneys)
- IV injection (Assist,Parvolex, Acetadote) – treatment of paracetamol/acetaminophen overdose
- Oral solution – various indications.
- Effervescent Tablets (200 mg) - Reolin (Hochland Pharma Germany), Solmucol (600 mg)(IBSA, Switzerland), Cystaline (Thailand), Mucinac (Cipla India), Siran (MegaPharm, Israel / Temmler Pharma, Germany), Amuco200 (Camox Pharmaceuticals, South Africa), ACC200 (Hexal Pharma, South Africa).
- Ocular solution - for mucolytic therapy
- Sachet (600 mg) - Bilim Pharmaceuticals, trebon N (Uni-Pharma Greece)
- CysNAC (900 mg) – NeuroScience Inc.
- PharmaNAC Effervescent Tablets (900 mg) - Bioadvantex Pharma.
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.
The following uses have not been well-established nor investigated:
- Acetylcysteine is being tested in a double blind trial in Systemic Lupus Erythematosus. The objective is to correct mitochondrial dysfunction.
- It may reduce the incidence of chronic obstructive pulmonary disease (COPD) exacerbations.
- In the treatment of AIDS, acetylcysteine has been shown to cause a "marked increase in immunological functions and plasma albumin concentrations".
Albumin concentration are inversely correlated with muscle wasting (cachexia), a condition associated with AIDS.
- A human study of 262 primarily elderly individuals indicates that acetylcysteine may decrease influenza symptoms. In the study, 25% of virus-infected subjects who received acetylcysteine treatment developed symptoms whereas 79% in the placebo group developed symptoms.
- Stability studies of carbocisteine in two differet dosage form, tablets and capsules.
- It has been suggested that acetylcysteine may help sufferers of Samter's triad by increasing levels of glutathione allowing faster breakdown of salicylates, though there is no evidence that it is of benefit.
- There are claims that acetylcysteine taken together with vitamin C and B1 can be used to prevent and relieve symptoms of veisalgia (hangover following ethanol (alcohol) consumption). The claimed mechanism is through scavenging of acetaldehyde, a toxic intermediate in the metabolism of ethanol. A rodent study found that while pretreatment with acetylcysteine protected against ethanol-induced liver damage, post-treatment actually worsened ethanol-induced liver damage.
- 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 sufferers of 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 patients suffering from 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 appears to improve the clinical efficacy of B vitamins in patients with raised homocysteine and memory disorders, including dementia.
- "L-Cysteine, N-acetyl- - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 25 March 2005. Identification. Retrieved 9 January 2012.
- "ACETYLCYSTEINE solution [Fresenius Kabi USA, LLC]". DailyMed. Fresenius Kabi USA, LLC. September 2013. Retrieved 8 November 2013.
- "ACETADOTE (acetylcysteine) injection, solution [Cumberland Pharmaceuticals Inc.]". DailyMed. Cumberland Pharmaceuticals Inc. June 2013. Retrieved 8 November 2013.
- "Acetylcysteine". Martindale: The Complete Drug Reference (The Royal Pharmaceutical Society of Great Britain). 16 November 2012. Retrieved 8 November 2013.
- "PRODUCT INFORMATION ACETADOTE® CONCENTRATED INJECTION" (PDF). TGA eBusiness Services. Phebra Pty Ltd. 16 January 2013. Retrieved 8 November 2013.
- Borgström L, Kågedal B, Paulsen O (1986). "Pharmacokinetics of N-acetylcysteine in man". Eur. J. Clin. Pharmacol. 31 (2): 217–22. doi:10.1007/BF00606662. PMID 3803419.
- Geier DA, Geier MR (2006). "A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders". Horm. Res. 66 (4): 182–8. doi:10.1159/000094467. PMID 16825783.
- 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.". West J Emerg Med 3: 218-26. PMID 23687539.
- "Acetadote Package Insert". FDA. Retrieved 19 April 2014.
- Dilger RN, Baker DH (2007). "Oral N-acetyl-L-cysteine is a safe and effective precursor of cysteine". J. Anim. Sci. 85 (7): 1712–8. doi:10.2527/jas.2006-835. PMID 17371789.
- Kanter MZ (2006). "Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning". Am J Health Syst Pharm 63 (19): 1821–7. doi:10.2146/ajhp060050. PMID 16990628.
- Dawson AH, Henry DA, McEwen J (1989). "Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning". Med. J. Aust. 150 (6): 329–31. PMID 2716644.
- Bailey B, McGuigan MA (1998). "Management of anaphylactoid reactions to intravenous N-acetylcysteine". Ann Emerg Med 31 (6): 710–5. doi:10.1016/S0196-0644(98)70229-X. PMID 9624310.
- Schmidt LE, Dalhoff K (2001). "Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning". Br J Clin Pharmacol 51 (1): 87–91. doi:10.1046/j.1365-2125.2001.01305.x. PMC 2014432. PMID 11167669.
- Lynch RM, Robertson R (2004). "Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study". Accid Emerg Nurs 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.
- Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA (2006). "High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis". Proc. Natl. Acad. Sci. U.S.A. 103 (12): 4628–33. doi:10.1073/pnas.0511304103. PMC 1450222. PMID 16537378.
- Tse, HN; Raiteri, L, Wong, K. Y, Yee, K. S, et al. (2013). "High-dose N-acetylcysteine in stable COPD: The 1-year, double-blind, randomized, placebo-controlled HIACE study". Chest 144 (1): 106–118. PMID 23348146.
- Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W (2000). "Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine". N. Engl. J. Med. 343 (3): 180–4. doi:10.1056/NEJM200007203430304. PMID 10900277.
- Hoffmann U, Fischereder M, Krüger B, Drobnik W, Krämer BK (2004). "The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable". J. Am. Soc. Nephrol. 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 (2004). "N-acetylcysteine reduces contrast-associated nephropathy but not clinical events during long-term follow-up". Am. Heart J. 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 (2006). "N-acetylcysteine and contrast-induced nephropathy in primary angioplasty". N. Engl. J. Med. 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 (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. 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. Retrieved 19 April 2014.
- Palma PC, Villaça Júnior CJ, Netto Júnior NR (1986). "N-acetylcysteine in the prevention of cyclophosphamide induced haemorrhagic cystitis". Int Surg 71 (1): 36–7. PMID 3522468.
- Hemorrhagic Cystitis Treatment & Management http://emedicine.medscape.com/article/2056130-treatment#aw2aab6b5b4
- Buijtels, PC; Petit, PL (2005). "Comparison of NaOH-< i> N-acetyl cysteine and sulfuric acid decontamination methods for recovery of mycobacteria from clinical specimens". Journal of Microbiological Methods 62 (1): 83–88. PMID 15823396.
- Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J (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". Biochem. Pharmacol. 79 (3): 413–20. doi:10.1016/j.bcp.2009.08.025. PMID 19732754.
- Kasielski M, Nowak D (2001). "Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease". Respir Med 95 (6): 448–56. doi:10.1053/rmed.2001.1066. PMID 11421501.
- Grandjean EM, Berthet P, Ruffmann R, Leuenberger P (2000). "Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials". Clin Ther 22 (2): 209–21. doi:10.1016/S0149-2918(00)88479-9. PMID 10743980.
- Stey C, Steurer J, Bachmann S, Medici TC, Tramèr MR (2000). "The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review". Eur. Respir. J. 16 (2): 253–62. doi:10.1034/j.1399-3003.2000.16b12.x. PMID 10968500.
- Poole PJ, Black PN (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.
- Meyer, A; Buhl, R., & Magnussen, H (1994). "The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis.". The European Respiratory Journal 7 (3): 431–436.
- Dean O, Giorlando F, Berk M (2011). "N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action". J Psychiatry Neurosci 36 (2): 78–86. doi:10.1503/jpn.100057. PMC 3044191. PMID 21118657.
- Berk M, Malhi GS, Gray LJ, Dean OM (2013). "The promise of N-acetylcysteine in neuropsychiatry". Trends Pharmacol. Sci. 34 (3): 167–77. doi:10.1016/j.tips.2013.01.001. PMID 23369637.
- Bavarsad Shahripour, R.; Harrigan, M. R.; Alexandrov, A. V. (2014). "N-acetylcysteine (NAC) in neurological disorders: Mechanisms of action and therapeutic opportunities". Brain and Behavior 4 (2): 108. doi:10.1002/brb3.208.
- Berk, M; Malhi, GS; Gray, LJ; Dean, OM (May 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.
- Samuni, Y; Goldstein, S; Dean, OM; Berk, M (August 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.
- Dean, O; Giorlando, F; Berk, M (March 2011). "N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action." (PDF). Journal of Psychiatry & Neuroscience 36 (2): 78–86. doi:10.1503/jpn.100057. PMC 3044191. PMID 21118657.
- Molina V, Papiol S, Sanz J, Rosa A, Arias B, Fatjó-Vilas M, Calama J, Hernández AI, Bécker J, Fañanás L (2011). "Convergent evidence of the contribution of TP53 genetic variation (Pro72Arg) to metabolic activity and white matter volume in the frontal lobe in schizophrenia patients". Neuroimage 56 (1): 45–51. doi:10.1016/j.neuroimage.2011.01.076. PMID 21296169.
- Gassó P, Mas S, Molina O, Lafuente A, Bernardo M, Parellada E (2014). "Increased susceptibility to apoptosis in cultured fibroblasts from antipsychotic-naïve first-episode schizophrenia patients". J Psychiatr Res 48 (1): 94–101. doi:10.1016/j.jpsychires.2013.09.017. PMID 24128664.
- Ni X, Trakalo J, Valente J, Azevedo MH, Pato MT, Pato CN, Kennedy JL (2005). "Human p53 tumor suppressor gene (TP53) and schizophrenia: case-control and family studies". Neurosci. Lett. 388 (3): 173–8. doi:10.1016/j.neulet.2005.06.050. PMID 16039051.
- Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I (2013). "Autophagy has a key role in the pathophysiology of schizophrenia". Mol. Psychiatry. doi:10.1038/mp.2013.174. PMID 24365867.
- Berk, M; Malhi, GS, Gray, LJ, Dean, OM (2013). "The promise of N-acetylcysteine in neuropsychiatry". Trends in Pharmacological Sciences 34 (3): 167–177. PMID 23369637.
- Oner G, Muderris II (2011). "Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome". Eur. J. Obstet. Gynecol. Reprod. Biol. 159 (1): 127–31. doi:10.1016/j.ejogrb.2011.07.005. PMID 21831508.
- 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.
- Eakin, K.; Baratz-Goldstein, R.; Pick, C.; Zindel, O.; Balaban, C.; Hoffer, M.; Lockwood, M.; Miller, J. et al. (2014). "Efficacy of N-Acetyl Cysteine in Traumatic Brain Injury". PLoS ONE.
- Chen, G.; Shi, J.; Hu, Z.; Hang, C. (2008). "Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine". Mediators of Inflammation 2008: 1. doi:10.1155/2008/716458.
- Abdel Baki, S. G.; Schwab, B.; Haber, M.; Fenton, A. A.; Bergold, P. J. (2010). "Minocycline Synergizes with N-Acetylcysteine and Improves Cognition and Memory Following Traumatic Brain Injury in Rats". PLoS ONE 5 (8): e12490. doi:10.1371/journal.pone.0012490.
- Haber, M.; Abdel Baki, S. G.; Grin'Kina, N. M.; Irizarry, R.; Ershova, A.; Orsi, S.; Grill, R. J.; Dash, P.; Bergold, P. J. (2013). "Minocycline plus N-acetylcysteine synergize to modulate inflammation and prevent cognitive and memory deficits in a rat model of mild traumatic brain injury". Experimental Neurology 249: 169. doi:10.1016/j.expneurol.2013.09.002.
- Şenol, N. N.; Nazıroğlu, M.; Yürüker, V. (2014). "N-Acetylcysteine and Selenium Modulate Oxidative Stress, Antioxidant Vitamin and Cytokine Values in Traumatic Brain Injury-Induced Rats". Neurochemical Research. doi:10.1007/s11064-014-1255-9.
- Yi, J. H.; Hoover, R.; McIntosh, T. K.; Hazell, A. S. (2006). "Early, Transient Increase in Complexin I and Complexin II in the Cerebral Cortex following Traumatic Brain Injury is Attenuated by N-Acetylcysteine". Journal of Neurotrauma 23: 86. doi:10.1089/neu.2006.23.86.
- Yi, J. H.; Hazell, A. S. (2005). "N-acetylcysteine attenuates early induction of heme oxygenase-1 following traumatic brain injury". Brain Research 1033: 13. doi:10.1016/j.brainres.2004.10.055.
- Xiong, Y; Peterson, P. L.; Lee, C. P. (1999). "Effect of N-acetylcysteine on mitochondrial function following traumatic brain injury in rats". Journal of neurotrauma 16 (11): 1067–82. PMID 10595823.
- Karalija, A.; Novikova, L. N.; Kingham, P. J.; Wiberg, M.; Novikov, L. N. (2012). "Neuroprotective Effects of N-Acetyl-Cysteine and Acetyl-L-Carnitine after Spinal Cord Injury in Adult Rats". PLoS ONE 7 (7): e41086. doi:10.1371/journal.pone.0041086.
- Cuzzocrea S, Mazzon E, Costantino G, Serraino I, Dugo L, Calabrò G, Cucinotta G, De Sarro A, Caputi AP (2000). "Beneficial effects of n-acetylcysteine on ischaemic brain injury". Br. J. Pharmacol. 130 (6): 1219–26. doi:10.1038/sj.bjp.0703421. PMC 1572181. PMID 10903958.
- Khan M, Sekhon B, Jatana M, Giri S, Gilg AG, Sekhon C, Singh I, Singh AK (2004). "Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke". J. Neurosci. Res. 76 (4): 519–27. doi:10.1002/jnr.20087. PMID 15114624.
- Sekhon B, Sekhon C, Khan M, Patel SJ, Singh I, Singh AK (2003). "N-Acetyl cysteine protects against injury in a rat model of focal cerebral ischemia". Brain Res. 971 (1): 1–8. doi:10.1016/S0006-8993(03)02244-3. PMID 12691831.
- "Mucomyst Package Insert". Retrieved 20 April 2014.
- Bjelakovic G, Nikolova D, Gluud C (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 (2012). "Does Nrf2 contribute to p53-mediated control of cell survival and death?". Antioxid. Redox Signal. 17 (12): 1670–5. doi:10.1089/ars.2012.4674. PMC 3474188. PMID 22559194.
- Bensaad K, Vousden KH (2005). "Savior and slayer: the two faces of p53". Nat. Med. 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 (2006). "p53 suppresses the Nrf2-dependent transcription of antioxidant response genes". J. Biol. Chem. 281 (52): 39776–84. doi:10.1074/jbc.M605707200. PMID 17077087.
- Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MO (2014). "Antioxidants accelerate lung cancer progression in mice". Sci Transl Med 6 (221): 221ra15. doi:10.1126/scitranslmed.3007653. PMID 24477002.
- Li J, Ghiani CA, Kim JY, Liu A, Sandoval J, DeVellis J, Casaccia-Bonnefil P (2008). "Inhibition of p53 transcriptional activity: a potential target for future development of therapeutic strategies for primary demyelination". J. Neurosci. 28 (24): 6118–27. doi:10.1523/JNEUROSCI.0184-08.2008. PMC 2962898. PMID 18550754.
- Laposa RR, Huang EJ, Cleaver JE (2007). "Increased apoptosis, p53 up-regulation, and cerebellar neuronal degeneration in repair-deficient Cockayne syndrome mice". Proc. Natl. Acad. Sci. U.S.A. 104 (4): 1389–94. doi:10.1073/pnas.0610619104. PMC 1783131. PMID 17229834.
- La Spada AR, Morrison RS (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 (2007). "S-nitrosothiols signal hypoxia-mimetic vascular pathology". J. Clin. Invest. 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 (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 (2006). "A dual effect of N-acetylcysteine on acute ethanol-induced liver damage in mice". Hepatol. Res. 34 (3): 199–206. doi:10.1016/j.hepres.2005.12.005. PMID 16439183.
- Dodd S, Dean O, Copolov DL, Malhi GS, Berk M (2008). "N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility". Expert Opin Biol Ther 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 (2012). "The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine". Biol. Psychiatry 71 (11): 978–86. doi:10.1016/j.biopsych.2011.10.024. PMC 3340445. PMID 22137594.
- 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 (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.
- 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.
- ClinicalTrials.gov NCT00775476 Treatment of Systemic Lupus Erythematosus (SLE) with N-Aetyl Cysteine (NAC)
- Pela R, Calcagni AM, Subiaco S, Isidori P, Tubaldi A, Sanguinetti CM (1999). "N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD". Respiration 66 (6): 495–500. doi:10.1159/000029447. PMID 10575333.
- Breitkreutz R, Pittack N, Nebe CT, Schuster D, Brust J, Beichert M, Hack V, Daniel V, Edler L, Dröge W (2000). "Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials". J. Mol. Med. 78 (1): 55–62. doi:10.1007/s001090050382. PMID 10759030.
- De Flora S, Grassi C, Carati L (1997). "Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment". Eur. Respir. J. 10 (7): 1535–41. doi:10.1183/09031936.97.10071535. PMID 9230243.
- Bachert C, Hörmann K, Mösges R, Rasp G, Riechelmann H, Müller R, Luckhaupt H, Stuck BA, Rudack C (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.
- Fowkes, Steven (13 December 1996). "Living with alcohol". Smart Drug News 5. Retrieved 2012-03-02.
- Ozaras R, Tahan V, Aydin S, Uzun H, Kaya S, Senturk H (January 2003). "N-acetylcysteine attenuates alcohol-induced oxidative stress in the rat". World J. Gastroenterol. 9 (1): 125–8. PMID 12508366.[unreliable medical source]
- Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A (2002). "N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome". Fertil. Steril. 77 (6): 1128–35. doi:10.1016/S0015-0282(02)03133-3. PMID 12057717.
- Aitio ML (2006). "N-acetylcysteine -- passe-partout or much ado about nothing?". Br J Clin Pharmacol 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 (1974). "Management of the dry eye in Sjogren's syndrome". Br J Ophthalmol 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 (2002). "N-acetylcysteine and Unverricht-Lundborg disease: variable response and possible side effects". Neurology 59 (9): 1447–9. PMID 12427904. Lay summary – Medscape.
- 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 (2011). "Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis". N. Engl. J. Med. 365 (19): 1781–9. doi:10.1056/NEJMoa1101214. PMID 22070475.
- McCaddon A (2006). "Homocysteine and cognitive impairment; a case series in a General Practice setting". Nutr J 5: 6. doi:10.1186/1475-2891-5-6. PMC 1395322. PMID 16480506.