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Identification
NameAcetylcysteine
Accession NumberDB06151
Typesmall molecule
Groupsapproved
Description

Acetylcysteine (also known as N-acetylcysteine or N-acetyl-L-cysteine or NAC) is primarily used as a mucolytic agent and in the management of acetaminophen poisoning. It is a derivative of cysteine with an acetyl group attached to the amino group of cysteine. NAC is essentially a prodrug that is converted to cysteine (in the intestine by the enzyme aminoacylase 1) and absorbed in the intestine into the blood stream. Cysteine is a key constituent to glutathione and hence administration of acetylcysteine replenishes glutathione stores. Acetylcysteine can also be used as a general antioxidant which can help mitigate symptoms for a variety of diseases exacerbated by reactive oxygen species (ROS). For instance, acetylcysteine is commonly used in individuals with renal impairment to prevent the precipitation of acute renal failure. Acetylcysteine has been shown to have efficacy in treating mild to moderate traumatic brain injury including ischemic brain injury, particularly in reducing neuronal losses, and also reducing cognitive and neurological symptoms when administered promptly after injury. N-acetylcysteine is now widely used in the treatment of HIV, and it has reported efficacy in chronic obstructive pulmonary disease and contrast-induced nephropathy. Acetylcysteine is also being successfully used to treat a variety of neuropsychiatric and neurodegenerative disorders including cocaine, cannabis, and smoking addictions, Alzheimer’s and Parkinson’s diseases, autism, compulsive and grooming disorders, schizophrenia, depression, and bipolar disorder. Recent data also shows that N-acetylcysteine inhibits muscle fatigue and can be used to enhance performance in endurance events and in exercise and endurance training.

Structure
Thumb
Synonyms
SynonymLanguageCode
N-acetylcysteineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AcetadoteNot Available
FluimucilNot Available
LysoxNot Available
MucolysinZambon
MucomystMead Johnson
ParvolexNot Available
Brand mixturesNot Available
Categories
CAS number616-91-1
WeightAverage: 163.195
Monoisotopic: 163.030313849
Chemical FormulaC5H9NO3S
InChI KeyPWKSKIMOESPYIA-BYPYZUCNSA-N
InChI
InChI=1S/C5H9NO3S/c1-3(7)6-4(2-10)5(8)9/h4,10H,2H2,1H3,(H,6,7)(H,8,9)/t4-/m0/s1
IUPAC Name
(2R)-2-acetamido-3-sulfanylpropanoic acid
SMILES
CC(=O)N[C@@H](CS)C(O)=O
Mass Specshow(8.35 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentN-acyl-alpha Amino Acids
Alternative parentsSecondary Carboxylic Acid Amides; Enolates; Polyamines; Carboxylic Acids; Alkylthiols
Substituentscarboxamide group; secondary carboxylic acid amide; alkylthiol; polyamine; enolate; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the n-acyl-alpha amino acids. These are compounds containing an alpha amino acid which bears an acyl group at his terminal nitrogen atom.
Pharmacology
IndicationAcetylcysteine is used mainly as a mucolytic and in the management of paracetamol (acetaminophen) overdose.
PharmacodynamicsAcetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. It is most effective when given early, with benefit seen principally in patients treated within 8-10 hours of the overdose. Acetylcysteine likely protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.
Mechanism of actionAcetylcysteine protects against acetaminophen overdose-induced hepatotoxicity by maintaining or restoring hepatic concentrations of glutathione. It does this by producing the glutathione precursor L-cysteine. Glutathione is required to inactivate an intermediate metabolite (N-acetyl-p-benzoquinoneimine or NAPQI) of acetaminophen that is thought to be hepatotoxic. In acetaminophen overdose cases, excessive quantities of this metabolite are formed because the primary metabolic (glucuronide and sulfate conjugation) pathways become saturated. Acetylcysteine may act by reducing the metabolite to the parent compound and/or by providing sulfhydryl for conjugation of the metabolite. Experimental evidence also suggests that a sulfhydryl-containing compound such as acetylcysteine may also directly inactivate the metabolite. The mechanisms of action for acetylcysteine’s well-known mucolytic effects are different. In particular, when inhaled, acetylcysteine (and its metabolic byproduct cysteine) exerts its mucolytic action through its free sulfhydryl group, which reduces the disulfide bonds in the mucus matrix and lowers mucus viscosity. This action increases with increasing pH and is most significant at pH 7 to 9. The mucolytic action of acetylcysteine is not affected by the presence of DNA. Acetylcysteine is also an antioxidant and reduces oxidative stress. 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. These effects on glutamate and NMDA signaling appear to explain some of the positive neuropsychotropic effects associated with NAC. Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB through redox activation of the nuclear factor kappa kinases thereby modulating cytokine synthesis.
AbsorptionBioavailability is 6–10% following oral administration and less than 3% following topical administration.
Volume of distributionNot Available
Protein binding83%
Metabolism

Hepatic. Deacetylated by the liver to cysteine and subsequently metabolized.

Route of eliminationNot Available
Half life5.6 hours (adults), 11 hours (neonates)
ClearanceNot Available
ToxicitySingle intravenous doses of acetylcysteine at 1000 mg/kg in mice, 2445 mg/kg in rats, 1500 mg/kg in guinea pigs, 1200 mg/kg in rabbits and 500 mg/kg in dogs were lethal. Symptoms of acute toxicity were ataxia, hypoactivity, labored respiration, cyanosis, loss of righting reflex and convulsions.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
Manufacturers
  • Cumberland pharmaceuticals inc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Roxane laboratories inc
  • Apothecon inc div bristol myers squibb
  • Dey lp
Packagers
Dosage forms
FormRouteStrength
LiquidRespiratory (inhalation)
SolutionRespiratory (inhalation)
Prices
Unit descriptionCostUnit
Mucomyst-10 10% Solution 30ml Vial25.99USDvial
Acetylcysteine 20% Solution 10ml Vial22.99USDvial
Acetylcysteine 10% Solution 30ml Vial19.99USDvial
Mucomyst 20% Solution 30ml Vial18.99USDvial
Acetylcysteine 20% Solution 30ml Vial17.99USDvial
Acetylcysteine 20% Solution 4ml Vial16.99USDvial
Acetylcysteine 10% Solution 10ml Vial8.66USDvial
Acetadote 200 mg/ml vial6.65USDml
Acetylcysteine powder3.07USDg
N-acetyl-l-cysteine powder0.84USDg
Mucomyst 20 % Solution0.75USDml
Acetylcysteine 20 % Solution0.68USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point109-110Martin, T.A. and Waller, C.W.; US. Patent 3,184,505; May 18, 1965; assigned to Mead Johnson & Company.
pKa9.52 (at 25 °C)SERJEANT & DEMPSEY (1979)
Predicted Properties
PropertyValueSource
water solubility5.09e+00 g/lALOGPS
logP-0.03ALOGPS
logP-0.71ChemAxon
logS-1.5ALOGPS
pKa (strongest acidic)3.82ChemAxon
pKa (strongest basic)-1.5ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count3ChemAxon
polar surface area66.4ChemAxon
rotatable bond count3ChemAxon
refractivity37.67ChemAxon
polarizability15.34ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MSMS/MS1D NMR2D NMR
References
Synthesis Reference

Rolf-Dieter Juch, Gerd Birrenbach, Christian Pflugshaupt, “Solid, fast-soluble pharmaceutical preparation containing S-(carboxymethyl)-L-cysteine and/or N-acetylcysteine.” U.S. Patent US5401514, issued November, 1990.

US5401514
General Reference
  1. Bachert C, Hormann K, Mosges R, Rasp G, Riechelmann H, Muller R, Luckhaupt H, Stuck BA, Rudack C: An update on the diagnosis and treatment of sinusitis and nasal polyposis. Allergy. 2003 Mar;58(3):176-91. Pubmed
  2. Bailey B, McGuigan MA: Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med. 1998 Jun;31(6):710-5. Pubmed
  3. Breitkreutz R, Pittack N, Nebe CT, Schuster D, Brust J, Beichert M, Hack V, Daniel V, Edler L, Droge W: Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials. J Mol Med. 2000;78(1):55-62. Pubmed
  4. Dawson AH, Henry DA, McEwen J: Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. Med J Aust. 1989 Mar 20;150(6):329-31. Pubmed
  5. Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A: N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002 Jun;77(6):1128-35. Pubmed
  6. Jones AL: Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol. 1998;36(4):277-85. Pubmed
External Links
ResourceLink
KEGG DrugD00221
KEGG CompoundC06809
PubChem Compound12035
PubChem Substance99443235
ChemSpider11540
ChEBI28939
ChEMBLCHEMBL600
Therapeutic Targets DatabaseDNC000981
PharmGKBPA448033
HETSC2
Drug Product Database2091526
RxListhttp://www.rxlist.com/cgi/generic/acetylcysteine.htm
Drugs.comhttp://www.drugs.com/cdi/acetylcysteine-solution.html
WikipediaAcetylcysteine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(238 KB)
MSDSshow(59.9 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. NAPQI (N-acetyl-p-benzoquinone imine)

Kind: small molecule

Organism: Human

Pharmacological action: unknown

Actions: reducer

Components

Name UniProt ID Details

References:

  1. Jones AL: Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol. 1998;36(4):277-85. Pubmed
  2. Prescott LF, Critchley JA: The treatment of acetaminophen poisoning. Annu Rev Pharmacol Toxicol. 1983;23:87-101. Pubmed
  3. Marzullo L: An update of N-acetylcysteine treatment for acute acetaminophen toxicity in children. Curr Opin Pediatr. 2005 Apr;17(2):239-45. Pubmed

2. Aminoacylase-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: ligand

Components

Name UniProt ID Details
Aminoacylase-1 Q03154 Details

References:

  1. Uttamsingh V, Keller DA, Anders MW: Acylase I-catalyzed deacetylation of N-acetyl-L-cysteine and S-alkyl-N-acetyl-L-cysteines. Chem Res Toxicol. 1998 Jul;11(7):800-9. Pubmed

3. Inhibitor of nuclear factor kappa-B kinase subunit alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Inhibitor of nuclear factor kappa-B kinase subunit alpha O15111 Details

References:

  1. Oka S, Kamata H, Kamata K, Yagisawa H, Hirata H: N-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinases. FEBS Lett. 2000 Apr 28;472(2-3):196-202. Pubmed

4. Inhibitor of nuclear factor kappa-B kinase subunit beta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Inhibitor of nuclear factor kappa-B kinase subunit beta O14920 Details

References:

  1. Oka S, Kamata H, Kamata K, Yagisawa H, Hirata H: N-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinases. FEBS Lett. 2000 Apr 28;472(2-3):196-202. Pubmed

5. Glutathione synthetase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: stimulator

Components

Name UniProt ID Details
Glutathione synthetase P48637 Details

References:

  1. Martensson J, Gustafsson J, Larsson A: A therapeutic trial with N-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria). J Inherit Metab Dis. 1989;12(2):120-30. Pubmed

6. Cystine/glutamate transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: activator

Components

Name UniProt ID Details
Cystine/glutamate transporter Q9UPY5 Details

References:

  1. Dean O, Giorlando F, Berk M: N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011 Mar;36(2):78-86. doi: 10.1503/jpn.100057. Pubmed

7. Glutamate receptor ionotropic, NMDA 2B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: activator

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 2B Q13224 Details

References:

  1. Lipton SA, Choi YB, Takahashi H, Zhang D, Li W, Godzik A, Bankston LA: Cysteine regulation of protein function—as exemplified by NMDA-receptor modulation. Trends Neurosci. 2002 Sep;25(9):474-80. Pubmed

8. Glutamate receptor ionotropic, NMDA 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: activator

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 1 Q05586 Details

References:

  1. Lipton SA, Choi YB, Takahashi H, Zhang D, Li W, Godzik A, Bankston LA: Cysteine regulation of protein function—as exemplified by NMDA-receptor modulation. Trends Neurosci. 2002 Sep;25(9):474-80. Pubmed

9. Glutamate receptor ionotropic, NMDA 2A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: activator

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 2A Q12879 Details

References:

  1. Lipton SA, Choi YB, Takahashi H, Zhang D, Li W, Godzik A, Bankston LA: Cysteine regulation of protein function—as exemplified by NMDA-receptor modulation. Trends Neurosci. 2002 Sep;25(9):474-80. Pubmed

10. Glutamate receptor ionotropic, NMDA 2D

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: activator

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 2D O15399 Details

References:

  1. Lipton SA, Choi YB, Takahashi H, Zhang D, Li W, Godzik A, Bankston LA: Cysteine regulation of protein function—as exemplified by NMDA-receptor modulation. Trends Neurosci. 2002 Sep;25(9):474-80. Pubmed

11. Glutamate receptor ionotropic, NMDA 3A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: activator

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 3A Q8TCU5 Details

References:

  1. Lipton SA, Choi YB, Takahashi H, Zhang D, Li W, Godzik A, Bankston LA: Cysteine regulation of protein function—as exemplified by NMDA-receptor modulation. Trends Neurosci. 2002 Sep;25(9):474-80. Pubmed

Transporters

1. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. Daily A, Monks NR, Leggas M, Moscow JA: Abrogation of microcystin cytotoxicity by MAP kinase inhibitors and N-acetyl cysteine is confounded by OATPIB1 uptake activity inhibition. Toxicon. 2010 Apr 1;55(4):827-37. Epub 2009 Nov 24. Pubmed

2. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Aslamkhan AG, Han YH, Yang XP, Zalups RK, Pritchard JB: Human renal organic anion transporter 1-dependent uptake and toxicity of mercuric-thiol conjugates in Madin-Darby canine kidney cells. Mol Pharmacol. 2003 Mar;63(3):590-6. Pubmed

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Drug created on January 15, 2008 09:45 / Updated on March 10, 2014 11:08