Acetylcysteine

Acetylcysteine

Acetylcysteine(INN)
Systematic (IUPAC) name
(2R)-2-acetamido-3-sulfanylpropanoic acid[1]
Clinical data
Pronunciation
Trade names Acetadote, Fluimucil, Mucomyst, Parvolex
AHFS/Drugs.com
Licence data US Daily Med:
Pregnancy
category
  • AU: B2
  • US: B (No risk in non-human studies)
Legal status
Routes of
administration
Oral, injection, inhalation
Pharmacokinetic data
Bioavailability 10% (Oral)[2]
Protein binding 50 to 83%[3]
Metabolism Liver[3]
Biological half-life 5.6 hours[4]
Excretion Renal (30%),[3] faecal (3%)
Identifiers
CAS Registry Number  N
ATC code R05 S01 V03
PubChem CID:
DrugBank  Y
ChemSpider  N
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C5H9NO3S
Molecular mass 163.195
Physical data
Melting point 106 °C (223 °F)
Boiling point 108 °C (226 °F)
Solubility in water 200 mg/mL (20 °C)
 N   

Acetylcysteine, also known as N-acetylcysteine or N-acetyl-L-cysteine (NAC), is a health system.[6] It is available as a generic medication and is not very expensive.[7]

Contents

  • Uses 1
    • Paracetamol overdose 1.1
    • Mucolytic therapy 1.2
    • Nephroprotective agent 1.3
    • Hemorrhagic cystitis 1.4
    • Interstitial lung disease 1.5
    • Psychiatry 1.6
    • Microbiological use 1.7
    • Other uses 1.8
  • Adverse effects 2
  • Pharmacology 3
    • Pharmacodynamics 3.1
    • Pharmacokinetics 3.2
  • Chemistry 4
  • Dosage forms 5
  • Research 6
  • References 7
  • External links 8

Uses

Paracetamol overdose

Intravenous and oral formulations of acetylcysteine are available for the treatment of paracetamol (acetaminophen) overdose.[8] 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.[9] 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.[9] Research suggests that the rate of liver toxicity is approximately 3% when acetylcysteine is administered within 10 hours of overdose.[8]

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,[10] 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.[11] Oral acetylcysteine is identical in bioavailability to cysteine precursors.[11] 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.[12] 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.[13][14][15][16] 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.

Mucolytic therapy

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, pulmonary fibrosis, and inhalation injury in children who have burns. It is also used post-operatively, as a diagnostic aid, and in tracheotomy care. It may be considered ineffective in cystic fibrosis.[17] 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.[18] 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.[19]

Nephroprotective agent

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,[20] whereas others do not.[21][22] It has been concluded that

  1. "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."[23]
  2. "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"[24]

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%.[25]

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.[26]

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.[27][28]

Interstitial lung disease

Acetylcysteine is used in the treatment of interstitial lung disease to prevent disease progression.[29][30][31]

Psychiatry

N-acetylcysteine has been successfully tried as a treatment for a number of psychiatric disorders.[32][33][34] 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).[32][33][35][36][37][38] Evidence does not support the efficacy for N-acetylcysteine in treating addictions to gambling, methamphetamine, or nicotine.[35]

Acetylcysteine has also been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.[33]

Microbiological use

Acetylcysteine can be used in Petroff's method i.e. liquefaction and decontamination of sputum, in preparation for recovery of mycobacterium.[39] It also displays significant antiviral activity against the influenza A viruses.[40]

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.[41]

Other uses

Acetylcysteine is sold as a dietary supplement commonly claiming antioxidant and liver protecting effects.

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.[42]

Adverse effects

The most commonly reported adverse effects for IV formulations of acetylcysteine are rash, urticaria, and pruritis.[9] 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.[43]

Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.[43]

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.[44] 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.[45][46][47] 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.[48] 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.[49] in all cells; it is a dose dependent response, and the ability to manipulate cellular apoptosis and autophagy has many therapeutic benefits.[50][51][52][53] Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs.[54] 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. N-acetylcysteine showed pro-oxidant activity at low doses whereas at high antioxidant doses NAC inhibited mitochondrial metabolism and reduced their efficiency.[55]

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.[54][56] Nonetheless, positive effects on age-diminished control of respiration (the hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.[57]

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.[58]

Pharmacology

Pharmacodynamics

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.[59] 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.[60][61] Glutathione also modulates the NMDA receptor by acting at the redox site.[33][62] Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB and modulating cytokine synthesis.[33]

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.[63][64] At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex.[64] 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.[65] As such, since N-acetylcysteine is a prodrug of glutathione, it may modulate all of the aforementioned receptors as well.

Pharmacokinetics

Extensively liver metabolized; CYP450 minimal. Urine excretion 22-30% with a half-life of 5.6 hours in adults and 11 hours in neonates.

Chemistry

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 1 in 8 of water and 1 in 2 of ethanol. It is practically insoluble in chloroform and ether. Sigma has dissolved this product in water at 100 mg/mL with heating and obtained a clear, colorless solution.

Appearance: White to white with light yellow cast powder Melting Point: 109 - 110 °C pKa: 9.5 at 30 °C Optical rotation: +5 ° (c = 3% in water).[66]

Dosage forms

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)
  • IV injection (Assist,Parvolex, Acetadote) – treatment of paracetamol/acetaminophen overdose
  • Oral solution – various indications.
  • Effervescent Tablets (200 mg)
  • Ocular solution - for mucolytic therapy
  • Tablets - commonly 600 mg, 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.

Research

  • It is being studied in conditions, such as autism, where cysteine and related sulfur amino acids may be depleted.[67]
  • Acetylcysteine in a double-blind placebo-controlled trial appears to reduce the effects of blast induced mild traumatic brain and neurological injury in soldiers.[68] 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.[34]
  • 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.[69]
  • It has been shown to help women with PCOS (polycystic ovary syndrome) to reduce insulin problems and possibly improve fertility.[70]
  • Small studies have shown acetylcysteine to be of benefit to people with blepharitis.[71] and has been shown to reduce ocular soreness caused by Sjogren's syndrome.[72]
  • It has been shown effective in the treatment of [74][73]
  • 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.[75]
  • Acetylcysteine has been hypothesized to be beneficial in Parkinson's disease. It is currently undergoing clinical trials.[76][77][78]
  • It has been demonstrated to improve the volume, motility, and viscosity of semen, and may improve male fertility.[79]

References

  1. ^ "L-Cysteine, N-acetyl- - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 25 March 2005. Identification. Retrieved 9 January 2012. 
  2. ^ Stockley RA (2008). Chronic Obstructive Pulmonary Disease a Practical Guide to Management. Chichester: John Wiley & Sons. p. 750.  
  3. ^ a b c d e f "Acetylcysteine". The American Society of Health-System Pharmacists. Retrieved Aug 22, 2015. 
  4. ^ "ACETADOTE (acetylcysteine) injection, solution [Cumberland Pharmaceuticals Inc.]". DailyMed. Cumberland Pharmaceuticals Inc. June 2013. Retrieved 8 November 2013. 
  5. ^ Fischer J, Ganellin CR (2006). Analogue-Based Drug Discovery. Weinheim: Wiley-VCH. p. 544.  
  6. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  7. ^ Baker E (2014). Top 100 drugs : clinical pharmacology and practical prescribing. p. Acetylcysteine.  
  8. ^ a b 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.  
  9. ^ a b c "Acetadote Package Insert" (PDF). FDA. Retrieved 19 April 2014. 
  10. ^ Borgström L, Kågedal B, Paulsen O (1986). "Pharmacokinetics of N-acetylcysteine in man". European Journal of Clinical Pharmacology 31 (2): 217–22.  
  11. ^ a b 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.  
  12. ^ 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.  
  13. ^ 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.  
  14. ^ Bailey B, McGuigan MA (Jun 1998). "Management of anaphylactoid reactions to intravenous N-acetylcysteine". Annals of Emergency Medicine 31 (6): 710–5.  
  15. ^ 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.  
  16. ^ 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.  
  17. ^ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
  18. ^ Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA (Mar 2006). "High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis". Proceedings of the National Academy of Sciences of the United States of America 103 (12): 4628–33.  
  19. ^ Tse HN, Raiteri L, Wong KY, Yee KS, Ng LY, Wai KY, Loo CK, Chan MH (Jul 2013). "High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study". Chest 144 (1): 106–18.  
  20. ^ 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.  
  21. ^ 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.  
  22. ^ 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.  
  23. ^ 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.  
  24. ^ 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.  
  25. ^ "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.  
  26. ^ Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. "KDIGO Clinical Practice Guideline for Acute Kidney Injury" (PDF). Retrieved 19 April 2014. 
  27. ^ 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.  
  28. ^ Hemorrhagic Cystitis~treatment at eMedicine
  29. ^ 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.  
  30. ^ 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.  
  31. ^ Poole PJ, Black PN (May 2001). "Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review". Bmj 322 (7297): 1271–4.  
  32. ^ a b 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.  
  33. ^ a b c d e 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.  
  34. ^ a b 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.  
  35. ^ a b 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.  
  36. ^ 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.  
  37. ^ 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.  
  38. ^ 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.  
  39. ^ 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.  
  40. ^ 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.  
  41. ^ 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.  
  42. ^ 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.  
  43. ^ a b "Mucomyst Package Insert". Retrieved 20 April 2014. 
  44. ^ Bjelakovic G, Nikolova D, Gluud C (Sep 2013). "Antioxidant supplements to prevent mortality". Jama 310 (11): 1178–9.  
  45. ^ 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.  
  46. ^ Bensaad K, Vousden KH (Dec 2005). "Savior and slayer: the two faces of p53". Nature Medicine 11 (12): 1278–9.  
  47. ^ 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.  
  48. ^ 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.  
  49. ^ 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.  
  50. ^ 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.  
  51. ^ 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.  
  52. ^ 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.  
  53. ^ 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.  
  54. ^ a b 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.  
  55. ^ Sharaf, Mahmoud S.; van den Heuvel, Michael R.; Stevens, Don; Kamunde, Collins (2015-07-01). "Zinc and calcium modulate mitochondrial redox state and morphofunctional integrity". Free Radical Biology and Medicine 84: 142–153.  
  56. ^ "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."
  57. ^ 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.  
  58. ^ 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.  
  59. ^ "PRODUCT INFORMATION ACETADOTE® CONCENTRATED INJECTION" (PDF). TGA eBusiness Services. Phebra Pty Ltd. 16 January 2013. Retrieved 8 November 2013. 
  60. ^ 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.  
  61. ^ 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.  
  62. ^ 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.  
  63. ^ 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.  
  64. ^ a b Varga, V.; Jenei, Zs.; Janáky, R.; Saransaari, P.; Oja, S. S. (1997). Neurochemical Research 22 (9): 1165–1171.  
  65. ^ Oja, S (2000). "Modulation of glutamate receptor functions by glutathione". Neurochemistry International 37 (2-3): 299–306.  
  66. ^ "N-ACETYL-L-CYSTEINE Product Information" (PDF). Sigma. Sigma-aldrich. Retrieved 9 November 2014. 
  67. ^ 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.  
  68. ^ 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.  
  69. ^ 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.  
  70. ^ 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.  
  71. ^ Aitio ML (Jan 2006). "N-acetylcysteine -- passe-partout or much ado about nothing?". British Journal of Clinical Pharmacology 61 (1): 5–15.  
  72. ^ 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.  
  73. ^ 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.  
  74. ^ Ataxia with Identified Genetic and Biochemical Defects at eMedicine
  75. ^ 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.  
  76. ^ 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.  
  77. ^ N-Acetylcysteine for Neuroprotection in Parkinson's Disease (NAC for PD)
  78. ^ Repeated-Dose Oral N-acetylcysteine for the Treatment of Parkinson's Disease
  79. ^ Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ (19 January 2011). "Antioxidants for male subfertility". The Cochrane Database of Systematic Reviews (1): CD007411.  

External links

  • U.S. National Library of Medicine: Drug Information Portal - Acetylcysteine