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targets (4) enzymes (2)
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Identification
Name Fomepizole
Accession Number DB01213 (APRD00985)
Type small molecule
Groups approved
Description

Fomepizole is used as an antidote in confirmed or suspected methanol or ethylene glycol poisoning. Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
4-methylpyrazole
Fomepizol [INN-Spanish]
Fomepizole [USAN:INN]
Fomepizolum [INN-Latin]
Salts Not Available
Brand names
Name Company
Antizol
Brand mixtures Not Available
Categories
  • Antidotes
CAS number 7554-65-6
Weight Average: 82.1038
Monoisotopic: 82.053098202
Chemical Formula C4H6N2
InChI Key InChIKey=RIKMMFOAQPJVMX-UHFFFAOYSA-N
InChI
InChI=1S/C4H6N2/c1-4-2-5-6-3-4/h2-3H,1H3,(H,5,6)
Plain Text
IUPAC Name
4-methyl-1H-pyrazole
SMILES
CC1=CNN=C1
Plain Text
Mass Spec show (8.42 KB)
Taxonomy
Kingdom Organic
Classes
  • Pyrazoles
Substructures
  • Pyrazoles
  • Heterocyclic compounds
  • Aromatic compounds
Pharmacology
Indication Antizol is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis
Pharmacodynamics Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol is first metabolized to glycoaldehyde which then undergoes further oxidation to glycolate, glyoxylate, and oxalate. It is glycolate and oxalate that are primarily responsible for the metabolic acidosis and renal damage that are seen in ethylene glycol poisoning. {01}{03} Methanol is first metabolized to formaldehyde and then undergoes subsequent oxidation via formaldehyde dehydrogenase to become formic acid. It is formic acid that is primarily responsible for the metabolic acidosis and visual disturbances that are associated with methanol poisoning.
Mechanism of action Antizol (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.
Absorption Rapid and complete
Volume of distribution
  • 0.6 to 1.02 L/kg
Protein binding Not Available
Metabolism Primarily hepaticm the primary metabolite is 4-carboxypyrazole (approximately 80 to 85% of an administered dose). Other metabolites include 4-hydroxymethylpyrazole and the N -glucuronide conjugates of 4-carboxypyrazole and 4-hydroxymethylpyrazole.
Route of elimination In healthy volunteers, only 1-3.5% of the administered dose of Antizol® (7-20 mg/kg oral and IV) was excreted unchanged in the urine, indicating that metabolism is the major route of elimination. In humans, the primary metabolite of Antizol® is 4-carboxypyrazole (approximately 80-85% of administered dose), which is excreted in the urine. The metabolites of Antizol® are excreted renally.
Half life The plasma half-life of Antizol varies with dose, even in patients with normal renal function, and has not been calculated.
Clearance Not Available
Toxicity Headache, nausea, dizziness
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Paladin labs usa inc
  • Bioniche pharma usa llc
  • Navinta llc
  • Pharmaforce inc
  • Synerx pharma llc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Prices
Unit description Cost Unit
Antizol 1.5 gm/1.5 ml vial 1849.8 USD ml
Antizol 1 gm/ml vial 1516.5 USD ml
Fomepizole 1.5 gm/1.5 ml vial 1364.85 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7553863 2007-06-30 2027-06-30
Properties
State liquid
Experimental Properties
Property Value Source
melting point 25 °C Not Available
logP 0.9 Not Available
Predicted Properties
Property Value Source
water solubility 5.59e+02 g/l ALOGPS
logP 0.41 ALOGPS
logP 0.79 ChemAxon
logS 0.83 ALOGPS
pKa (strongest acidic) 15.82 ChemAxon
pKa (strongest basic) 2.13 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 1 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 28.68 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 24.79 ChemAxon
polarizability 8.58 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00707 Link_out
KEGG Compound C07837 Link_out
PubChem Compound 3406 Link_out
PubChem Substance 46508566 Link_out
ChemSpider 3289 Link_out
ChEBI 5141 Link_out
ChEMBL 5141 Link_out
Therapeutic Targets Database DAP000568 Link_out
PharmGKB PA449697 Link_out
Drug Product Database 2242980 Link_out
RxList http://www.rxlist.com/cgi/generic/antizol.htm Link_out
Drugs.com http://www.drugs.com/mtm/fomepizole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Fomepizole Link_out
ATC Codes
  • V03AB34
AHFS Codes
  • 92:00.00
PDB Entries Not Available
FDA label Not Available
MSDS show (64.1 KB)
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Alcohol dehydrogenase 1A

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: P07327 Link_out
Gene: ADH1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nagata H, Sekizuka E, Morishita T, Tatemichi M, Kurokawa T, Mizuki A, Ishii H: Adenosine A2-receptor mediates ethanol-induced arteriolar dilation in rat stomach. Am J Physiol. 1996 Dec;271(6 Pt 1):G1028-33. Pubmed
  2. Mukherjee PK, Mohamed S, Chandra J, Kuhn D, Liu S, Antar OS, Munyon R, Mitchell AP, Andes D, Chance MR, Rouabhia M, Ghannoum MA: Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanism. Infect Immun. 2006 Jul;74(7):3804-16. Pubmed
  3. Nussrallah BA, Dam R, Wagner FW: Characterization of Coturnix quail liver alcohol dehydrogenase enzymes. Biochemistry. 1989 Jul 25;28(15):6245-51. Pubmed
  4. Brent J: Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med. 2009 May 21;360(21):2216-23. Pubmed
  5. Calello DP, Osterhoudt KC, Henretig FM: New and novel antidotes in pediatrics. Pediatr Emerg Care. 2006 Jul;22(7):523-30. Pubmed
  6. Betten DP, Vohra RB, Cook MD, Matteucci MJ, Clark RF: Antidote use in the critically ill poisoned patient. J Intensive Care Med. 2006 Sep-Oct;21(5):255-77. Pubmed

2. Alcohol dehydrogenase 1B

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: P00325 Link_out
Gene: ADH1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yin SJ, Liao CS, Chen CM, Fan FT, Lee SC: Genetic polymorphism and activities of human lung alcohol and aldehyde dehydrogenases: implications for ethanol metabolism and cytotoxicity. Biochem Genet. 1992 Apr;30(3-4):203-15. Pubmed
  2. Eriksson CJ, Fukunaga T, Sarkola T, Chen WJ, Chen CC, Ju JM, Cheng AT, Yamamoto H, Kohlenberg-Muller K, Kimura M, Murayama M, Matsushita S, Kashima H, Higuchi S, Carr L, Viljoen D, Brooke L, Stewart T, Foroud T, Su J, Li TK, Whitfield JB: Functional relevance of human adh polymorphism. Alcohol Clin Exp Res. 2001 May;25(5 Suppl ISBRA):157S-163S. Pubmed
  3. Kassam JP, Tang BK, Kadar D, Kalow W: In vitro studies of human liver alcohol dehydrogenase variants using a variety of substrates. Drug Metab Dispos. 1989 Sep-Oct;17(5):567-72. Pubmed
  4. Brent J: Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med. 2009 May 21;360(21):2216-23. Pubmed
  5. Calello DP, Osterhoudt KC, Henretig FM: New and novel antidotes in pediatrics. Pediatr Emerg Care. 2006 Jul;22(7):523-30. Pubmed
  6. Betten DP, Vohra RB, Cook MD, Matteucci MJ, Clark RF: Antidote use in the critically ill poisoned patient. J Intensive Care Med. 2006 Sep-Oct;21(5):255-77. Pubmed

3. Alcohol dehydrogenase 1C

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: P00326 Link_out
Gene: ADH1C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Eriksson CJ, Fukunaga T, Sarkola T, Chen WJ, Chen CC, Ju JM, Cheng AT, Yamamoto H, Kohlenberg-Muller K, Kimura M, Murayama M, Matsushita S, Kashima H, Higuchi S, Carr L, Viljoen D, Brooke L, Stewart T, Foroud T, Su J, Li TK, Whitfield JB: Functional relevance of human adh polymorphism. Alcohol Clin Exp Res. 2001 May;25(5 Suppl ISBRA):157S-163S. Pubmed
  2. Brent J: Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med. 2009 May 21;360(21):2216-23. Pubmed
  3. Calello DP, Osterhoudt KC, Henretig FM: New and novel antidotes in pediatrics. Pediatr Emerg Care. 2006 Jul;22(7):523-30. Pubmed
  4. Betten DP, Vohra RB, Cook MD, Matteucci MJ, Clark RF: Antidote use in the critically ill poisoned patient. J Intensive Care Med. 2006 Sep-Oct;21(5):255-77. Pubmed

4. Catalase

Pharmacological action: yes
Actions: inhibitor

Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide

Organism class: human
UniProt ID: P04040 Link_out
Gene: CAT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thurman RG, McKenna WR, Brentzel HJ Jr, Hesse S: Significant pathways of hepatic ethanol metabolism. Fed Proc. 1975 Oct;34(11):2075-81. Pubmed
  2. Handler JA, Thurman RG: Catalase-dependent ethanol oxidation in perfused rat liver. Requirement for fatty-acid-stimulated H2O2 production by peroxisomes. Eur J Biochem. 1988 Sep 15;176(2):477-84. Pubmed
  3. Bradford BU, Forman DT, Thurman RG: 4-Methylpyrazole inhibits fatty acyl coenzyme synthetase and diminishes catalase-dependent alcohol metabolism: has the contribution of alcohol dehydrogenase to alcohol metabolism been previously overestimated? Mol Pharmacol. 1993 Jan;43(1):115-9. Pubmed
Enzymes

1. Cytochrome P450 2E1

Actions: inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2A6

Actions: inhibitor

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:20