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Identification
NameAllopurinol
Accession NumberDB00437  (APRD00435, DB03027)
Typesmall molecule
Groupsapproved
Description

A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
1,5-Dihydro-4H-pyrazolo(3,4-D)pyrimidin-4-oneNot AvailableNot Available
1,5-Dihydro-4H-pyrazolo(3,4-D)pyrimidine-4-oneNot AvailableNot Available
1H-Pyrazolo(3,4-D)pyrimidin-4-olNot AvailableNot Available
4-HPPNot AvailableNot Available
4-Hydroxy-1H-pyrazolo(3,4-D)pyrimidineNot AvailableNot Available
4-Hydroxy-3,4-pyrazolopyrimidineNot AvailableNot Available
4-Hydroxypyrazolo(3,4-D)pyrimidineNot AvailableNot Available
4-HydroxypyrazolopyrimidineNot AvailableNot Available
4-Hydroxypyrazolyl(3,4-D)pyrimidineNot AvailableNot Available
4'-Hydroxypyrazolol(3,4-D)pyrimidineNot AvailableNot Available
4H-Pyrazolo(3,4-D)pyrimidin-4-oneNot AvailableNot Available
AL-100Not AvailableNot Available
AllopurinolNot AvailableNot Available
AllopurinolumLatinINN
AlopurinolSpanishINN
Zyloprim (tn)Not AvailableNot Available
Salts
Name/CAS Structure Properties
Allopurinol Sodium
Thumb
  • InChI Key: PTJRZVJXXNYNLN-UHFFFAOYSA-M
  • Monoisotopic Mass: 158.020455413
  • Average Mass: 158.0933
DBSALT000350
Brand names
NameCompany
AdenockTanabe
AllohexalNot Available
AllorilNot Available
AloprimNot Available
AluronNot Available
MiluritNot Available
ProgoutNot Available
ZyloprimWellcome
ZyloricNot Available
ZyrikNot Available
Brand mixturesNot Available
Categories
CAS number315-30-0
WeightAverage: 136.1115
Monoisotopic: 136.03851077
Chemical FormulaC5H4N4O
InChI KeyOFCNXPDARWKPPY-UHFFFAOYSA-N
InChI
InChI=1S/C5H4N4O/c10-5-3-1-8-9-4(3)6-2-7-5/h1-2H,(H2,6,7,8,9,10)
IUPAC Name
1H,2H,4H-pyrazolo[3,4-d]pyrimidin-4-one
SMILES
O=C1N=CN=C2NNC=C12
Mass Specshow(7.32 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyrazolopyrimidines
SubclassNot Available
Direct parentPyrazolopyrimidines
Alternative parentsPyrimidones; Pyrazoles; Polyamines
Substituentspyrimidone; pyrimidine; pyrazole; azole; polyamine; organonitrogen compound
Classification descriptionThis compound belongs to the pyrazolopyrimidines. These are compounds containing a pyrazolopyrimidine skeleton, which consists of a pyrazole fused to a pyrimidine.
Pharmacology
IndicationFor the treatment of hyperuricemia associated with primary or secondary gout. Also indicated for the treatment of primary or secondary uric acid nephropathy, with or without the symptoms of gout, as well as chemotherapy-induced hyperuricemia and recurrent renal calculi.
PharmacodynamicsAllopurinol, a structural analog of the natural purine base hypoxanthine, is used to prevent gout and renal calculi due to either uric acid or calcium oxalate and to treat uric acid nephropathy, hyperuricemia, and some solid tumors.
Mechanism of actionAllopurinol and its active metabolite, oxypurinol, inhibits the enzyme xanthine oxidase, blocking the conversion of the oxypurines hypoxanthine and xanthine to uric acid. Elevated concentrations of oxypurine and oxypurine inhibition of xanthine oxidase through negative feedback results in a decrease in the concentrations of uric acid in the serum and urine. Allopurinol also facilitates the incorporation of hypoxanthine and xanthine into DNA and RNA, leading to a feedback inhibition of de novo purin synthesis and a decrease in serum uric acid concentrations as a result of an increase in nucleotide concentration.
AbsorptionApproximately 80-90% absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingAllopurinol and oxypurinol are not bound to plasma proteins
Metabolism

Hepatic

SubstrateEnzymesProduct
Allopurinol
oxypurinolDetails
Route of eliminationApproximately 20% of the ingested allopurinol is excreted in the feces.
Half life1-3 hours
ClearanceNot Available
ToxicityLD50=214 mg/kg (in mice)
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 + 0.997
Blood Brain Barrier + 0.9885
Caco-2 permeable - 0.6232
P-glycoprotein substrate Non-substrate 0.7409
P-glycoprotein inhibitor I Non-inhibitor 0.9135
P-glycoprotein inhibitor II Non-inhibitor 0.9858
Renal organic cation transporter Non-inhibitor 0.8653
CYP450 2C9 substrate Non-substrate 0.8635
CYP450 2D6 substrate Non-substrate 0.8256
CYP450 3A4 substrate Non-substrate 0.6242
CYP450 1A2 substrate Non-inhibitor 0.8817
CYP450 2C9 substrate Non-inhibitor 0.9472
CYP450 2D6 substrate Non-inhibitor 0.923
CYP450 2C19 substrate Non-inhibitor 0.9198
CYP450 3A4 substrate Non-inhibitor 0.858
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9169
Ames test Non AMES toxic 0.7089
Carcinogenicity Non-carcinogens 0.921
Biodegradation Not ready biodegradable 0.9675
Rat acute toxicity 2.1087 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9511
hERG inhibition (predictor II) Non-inhibitor 0.9448
Pharmacoeconomics
Manufacturers
  • Apotex inc etobicoke site
  • Caraco pharmaceutical laboratories ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Northstar healthcare holdings ltd
  • Par pharmaceutical inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Superpharm corp
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • Abbott laboratories pharmaceutical products div
  • Dr reddys laboratories louisiana llc
  • Prometheus laboratories inc
  • Bedford laboratories
  • Bioniche pharma usa llc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Aloprim 500 mg vial612.3USDvial
Allopurinol sodium 500 mg vial583.14USDvial
Allopurinol powder18.41USDg
Zyloprim 300 mg tablet1.89USDtablet
Zyloprim 100 mg tablet0.82USDtablet
Allopurinol 300 mg tablet0.46USDtablet
Allopurinol 100 mg tablet0.24USDtablet
Apo-Allopurinol 300 mg Tablet0.22USDtablet
Novo-Purol 300 mg Tablet0.22USDtablet
Apo-Allopurinol 200 mg Tablet0.14USDtablet
Novo-Purol 200 mg Tablet0.14USDtablet
Apo-Allopurinol 100 mg Tablet0.08USDtablet
Novo-Purol 100 mg Tablet0.08USDtablet
Suspendol-s liquid0.04USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point350 °CPhysProp
water solubility569 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.55BUNDGAARD,H & FALCH,E (1985)
logS-2.38ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility5.88e+00 g/lALOGPS
logP-1.7ALOGPS
logP-1.8ChemAxon
logS-1.4ALOGPS
pKa (strongest acidic)7.83ChemAxon
pKa (strongest basic)2.57ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count2ChemAxon
polar surface area65.85ChemAxon
rotatable bond count0ChemAxon
refractivity54.24ChemAxon
polarizability11.67ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Druey, J. and Schmidt, P.; US. Patent 2868,803; January 13,1959; assigned to Ciba Pharmaceutical Products Inc.
Hitchings, G.H. and Falco, EA.; U.S. Patent 3,474,098; October 21,1969; assigned to Bur-
roughs Wellcome & Co.
Cresswell, R.M.and Mentha, J.W.; US.Patent4,146,713; March27,1979; assigned to Bur-
roughs Wellcome & Co.

General Reference
  1. Pacher P, Nivorozhkin A, Szabo C: Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006 Mar;58(1):87-114. Pubmed
  2. Schlesinger N: Diagnosing and treating gout: a review to aid primary care physicians. Postgrad Med. 2010 Mar;122(2):157-61. Pubmed
  3. Suzuki I, Yamauchi T, Onuma M, Nozaki S: Allopurinol, an inhibitor of uric acid synthesis—can it be used for the treatment of metabolic syndrome and related disorders? Drugs Today (Barc). 2009 May;45(5):363-78. Pubmed
  4. Terkeltaub R: Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol. 2010 Jan;6(1):30-8. Pubmed
  5. George J, Struthers AD: Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag. 2009;5(1):265-72. Epub 2009 Apr 8. Pubmed
External Links
ResourceLink
KEGG DrugD00224
PubChem Compound2094
PubChem Substance46508516
ChemSpider2010
BindingDB50241255
ChEBI40279
ChEMBLCHEMBL1467
Therapeutic Targets DatabaseDAP000773
PharmGKBPA448320
HET7HP
Drug Product Database555681
RxListhttp://www.rxlist.com/cgi/generic/allopur.htm
Drugs.comhttp://www.drugs.com/allopurinol.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zyl1508.shtml
WikipediaAllopurinol
ATC CodesM04AA01
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelNot Available
MSDSshow(75.9 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolAllopurinol may increase the anticoagulant effect of acenocoumarol.
AnisindioneAllopurinol may increase the anticoagulant effect of anisindione.
AzathioprineAllopurinol may increase the effect of thiopurine, azathioprine.
CyclosporineAllopurinol increases the effect and toxicity of cyclosporine
DicoumarolAllopurinol may increase the anticoagulant effect of dicumarol.
MercaptopurineAllopurinol may increase the effect of thiopurine, mercaptopurine.
TrandolaprilThe ACE inhibitor, Trandolapril, may increase the risk of hypersensitivity reactions to Allopurinol.
WarfarinAllopurinol may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin times and therapeutic effects of warfarin if allopurinol is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water.
  • Take with food.

Targets

1. Xanthine dehydrogenase/oxidase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Xanthine dehydrogenase/oxidase P47989 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Suzuki I, Yamauchi T, Onuma M, Nozaki S: Allopurinol, an inhibitor of uric acid synthesis—can it be used for the treatment of metabolic syndrome and related disorders? Drugs Today (Barc). 2009 May;45(5):363-78. Pubmed
  3. Carro MD, Falkenstein E, Radke WJ, Klandorf H: Effects of allopurinol on uric acid concentrations, xanthine oxidoreductase activity and oxidative stress in broiler chickens. Comp Biochem Physiol C Toxicol Pharmacol. 2010 Jan;151(1):12-7. Epub 2009 Aug 3. Pubmed
  4. George J, Struthers AD: Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag. 2009;5(1):265-72. Epub 2009 Apr 8. Pubmed
  5. Higgins P, Dawson J, Walters M: The potential for xanthine oxidase inhibition in the prevention and treatment of cardiovascular and cerebrovascular disease. Cardiovasc Psychiatry Neurol. 2009;2009:282059. Epub 2009 Nov 4. Pubmed
  6. Dincer HE, Dincer AP, Levinson DJ: Asymptomatic hyperuricemia: to treat or not to treat. Cleve Clin J Med. 2002 Aug;69(8):594, 597, 600-2 passim. Pubmed
  7. Kelley WN, Wyngaarden JB: Effects of allopurinol and oxipurinol on purine synthesis in cultured human cells. J Clin Invest. 1970 Mar;49(3):602-9. Pubmed
  8. Okamoto K: [Inhibitors of xanthine oxidoreductase] Nippon Rinsho. 2008 Apr;66(4):748-53. Pubmed
  9. Taha MO, Simoes MJ, Noguerol EC, Mendonca FP, Pascoalick HM, Alves RA, Vivian ME, Morales FP, Campos AC, Magalhaes KG, Venerando PS, Tersariol IL, Monteiro HP, Oliveira-Junior IS, Jurkiewicz A, Caricati-Neto A: Effects of allopurinol on ischemia and reperfusion in rabbit livers. Transplant Proc. 2009 Apr;41(3):820-3. Pubmed
  10. Terkeltaub R: Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol. 2010 Jan;6(1):30-8. Pubmed
  11. Pacher P, Nivorozhkin A, Szabo C: Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006 Mar;58(1):87-114. Pubmed

Enzymes

1. Aldehyde oxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Aldehyde oxidase Q06278 Details

References:

  1. Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. Pubmed

2. Xanthine dehydrogenase/oxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Xanthine dehydrogenase/oxidase P47989 Details

References:

  1. Moriwaki Y, Yamamoto T, Nasako Y, Takahashi S, Suda M, Hiroishi K, Hada T, Higashino K: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase. Biochem Pharmacol. 1993 Sep 14;46(6):975-81. Pubmed

Transporters

1. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. Pubmed

2. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

References:

  1. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on March 27, 2014 13:14