DrugBank: Mefenamic acid (DB00784)

targets (2) enzymes (2)

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

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
	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
KEGG Compound	C02168
PubChem Compound	4044
PubChem Substance	46505405
ChemSpider	3904
BindingDB	50134036
Therapeutic Targets Database	DAP000779
PharmGKB	PA450347
Drug Product Database	2237826
RxList	http://www.rxlist.com/cgi/generic3/mefenamic.htm
Drugs.com	http://www.drugs.com/cdi/mefenamic-acid.html
Wikipedia	http://en.wikipedia.org/wiki/Mefenamic_acid

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 Gene: PTGS2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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 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 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 Gene: PTGS1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 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 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

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:

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
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
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
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
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
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:

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
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
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
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
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 Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 Gene: CYP2C8 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

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:

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
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:

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.