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Identification
Name Mefenamic acid
Accession Number DB00784 (APRD00730)
Type small molecule
Groups approved
Description

A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase. [PubChem]

Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Acide Mefenamique
  • Mefanamic Acid
  • Mefenacid
  • Mefenaminsaeure
  • Mephenamic Acid
  • Mephenaminic Acid
  • Methenamic Acid
Brand names
  • Bafameritin-M
  • Bafhameritin-M
  • Bonabol
  • Coslan
  • HL 1
  • In-M
  • Lysalgo
  • Mefacit
  • Namphen
  • Parkemed
  • Ponalar
  • Ponstan
  • Ponstan Forte
  • Ponstel
  • Ponstil
  • Ponstyl
  • Pontal
  • Tamany Bonsan
  • Tanston
  • Vialidon
Brand name mixtures Not Available
Categories
  • Cyclooxygenase Inhibitors
CAS number 61-68-7
Weight Average: 241.2851
Monoisotopic: 241.110278729
Chemical Formula C15H15NO2
InChI Key InChIKey=HYYBABOKPJLUIN-UHFFFAOYSA-N
InChI
InChI=1S/C15H15NO2/c1-10-6-5-9-13(11(10)2)16-14-8-4-3-7-12(14)15(17)18/h3-9,16H,1-2H3,(H,17,18)
Plain Text
IUPAC Name
2-[(2,3-dimethylphenyl)amino]benzoic acid
SMILES
CC1=CC=CC(NC2=C(C=CC=C2)C(O)=O)=C1C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aminobenzoates
Substructures
  • Aminobenzoates
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Benzoyl Derivatives
  • Anilines
Pharmacology
Indication For the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever.
Pharmacodynamics Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase.
Mechanism of action Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.
Absorption Mefenamic acid is rapidly absorbed after oral administration.
Volume of distribution
  • 1.06 L/kg [Normal Healthy Adults (18-45 yr)]
Protein binding 90%
Metabolism

Mefenamic acid undergoes metabolism by CYP2C9 to 3-hydroxymethyl mefenamic acid, and further oxidation to a 3-carboxymefenamic acid may occur. The activity of these metabolites has not been studied. Mefenamic acid is also glucuronidated directly.

Route of elimination The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination.
Half life 2 hours
Clearance
  • Oral cl=21.23 L/hr [Healthy adults (18-45 yrs)]
Toxicity Oral, rat LD50: 740 mg/kg. Symptoms of overdose may include severe stomach pain, coffee ground-like vomit, dark stool, ringing in the ears, change in amount of urine, unusually fast or slow heartbeat, muscle weakness, slow or shallow breathing, confusion, severe headache or loss of consciousness.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00109 Mefanamic Acid Pathway SMP00109
Pharmacoeconomics
Manufacturers
  • Shionogi pharma inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Ponstel 250 mg capsule 11.85 USD capsule
Mefenamic acid powder 2.85 USD g
Ponstel 250 mg kapseals 1.59 USD each
Apo-Mefenamic 250 mg Capsule 0.52 USD capsule
Patents Not Available
Properties
State solid
Melting point 230-231 oC
Experimental Properties
Property Value Source
water solubility 20 mg/L PhysProp
logP 4.2 PhysProp
logS -3.78 [ADME Research, USCD] PhysProp
pKa 4.2 Various sources
Predicted Properties
Property Value Source
water solubility 1.37e-02 g/l ALOGPS
logP 4.58 ALOGPS
logP 5.40 ChemAxon Molconvert
logS -4.25 ALOGPS
pKa 17.77 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 49.33 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 71.88 ChemAxon Molconvert
polarizability 26.22 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00151 Link_out
KEGG Compound C02168 Link_out
PubChem Compound 4044 Link_out
PubChem Substance 46505405 Link_out
ChemSpider 3904 Link_out
BindingDB 50134036 Link_out
Therapeutic Targets Database DAP000779 Link_out
PharmGKB PA450347 Link_out
Drug Product Database 2237826 Link_out
RxList http://www.rxlist.com/cgi/generic3/mefenamic.htm Link_out
Drugs.com http://www.drugs.com/cdi/mefenamic-acid.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mefenamic_acid Link_out
ATC Codes
  • M01AG01
AHFS Codes
  • 28:08.04.92
PDB Entries Not Available
FDA label show (134.9 KB)
MSDS show (59.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take with food.
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: yes
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Gierse JK, Hauser SD, Creely DP, Koboldt C, Rangwala SH, Isakson PC, Seibert K: Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem J. 1995 Jan 15;305 ( Pt 2):479-84. Pubmed
  2. Bhat AS, Tandan SK, Kumar D, Krishna V, Prakash VR: Interaction between inhibitors of inducible nitric oxide synthase and cyclooxygenase in adjuvant-induced arthritis in female albino rats: an isobolographic study. Eur J Pharmacol. 2007 Feb 5;556(1-3):190-9. Epub 2006 Oct 27. Pubmed
  3. Bhat AS, Tandan SK, Kumar D, Krishna V, Prakash VR: Interaction between inhibitors of inducible nitric oxide synthase and cyclooxygenase in Brewer’s yeast induced pyrexia in mice: an isobolographic study. Eur J Pharmacol. 2005 Mar 28;511(2-3):137-42. Pubmed
  4. Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21. Pubmed
  5. Walton LJ, Franklin IJ, Bayston T, Brown LC, Greenhalgh RM, Taylor GW, Powell JT: Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms. Circulation. 1999 Jul 6;100(1):48-54. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin G/H synthase 1

Pharmacological action: unknown
Actions: inhibitor

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sinniah R, Lye WC: Acute renal failure from hemoglobinuric and interstitial nephritis secondary to iodine and mefenamic acid. Clin Nephrol. 2001 Mar;55(3):254-8. Pubmed
  2. Joo Y, Kim HS, Woo RS, Park CH, Shin KY, Lee JP, Chang KA, Kim S, Suh YH: Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer’s disease models. Mol Pharmacol. 2006 Jan;69(1):76-84. Epub 2005 Oct 13. Pubmed
  3. Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21. Pubmed
  4. Gierse JK, Hauser SD, Creely DP, Koboldt C, Rangwala SH, Isakson PC, Seibert K: Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem J. 1995 Jan 15;305 ( Pt 2):479-84. Pubmed
  5. Laudanno OM, Cesolari JA, Esnarriaga J, Flaherty P, Vada J, Guastalli G, San Miguel P, Bedini OA: [In vivo selectivity of nonsteroidal anti-inflammatory drugs on COX-1-COX-2 and gastrointestinal ulcers, in rats] Acta Gastroenterol Latinoam. 1998;28(3):249-55. Pubmed

Enzymes

1. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. 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 2C8

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
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 November 10, 2010 13:42

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.