MEFENAMIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H15NO2
Molecular Weight	241.2851
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(C)C(NC2=CC=CC=C2C(O)=O)=CC=C1

InChI

InChIKey=HYYBABOKPJLUIN-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23656341

Mefenamic acid is a non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is used for the treatment of mild to moderate pain, including menstrual pain, inflammation, and fever. Clinical use of mefenamic acid has generally declined in an era where other NSAID use has flourished. While having modes of action and general toxicities similar to other NSAIDs, mefenamic acid, as a member of the fenamates, nevertheless possesses some unique in vitro effects that have the potential to distinguish this agent from others. Use of this drug remains relevant for pain syndromes and some gynecological disorders, albeit with considerable competition from other NSAIDs. New basic science has considerably improved the understanding of the biochemistry of mefenamic acid. As well as maintaining its use in traditional settings, there is a tremendous potential for expanding the application of mefenamic acid to niche roles. Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. Mefenamic acid concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because mefenamic acid is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-2 201 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9626023	Inhibitor 8504		2.9 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	Palliative		Approved 8583	PONSTEL Approved Use Mefenamic acid is indicated: For relief of mild to moderate pain in patients ≥ 14 years of age, when therapy will not exceed one week (7 days). For treatment of primary dysmenorrhea. Launch Date 1981
Primary dysmenorrhea 16 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	Palliative		Approved 8583	PONSTEL Approved Use Mefenamic acid is indicated: For relief of mild to moderate pain in patients ≥ 14 years of age, when therapy will not exceed one week (7 days). For treatment of primary dysmenorrhea. Launch Date 1981

C_max

Value	Dose	Co-administered	Analyte	Population
5.91 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22116543/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		MEFENAMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7942001/	2 mg/kg 1 times / day steady-state, oral dose: 2 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		MEFENAMIC ACID plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
38.03 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22116543/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		MEFENAMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22116543/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		MEFENAMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
18.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7942001/	2 mg/kg 1 times / day steady-state, oral dose: 2 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		MEFENAMIC ACID plasma	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		MEFENAMIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg 1 times / day steady, oral Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	Disc. AE: Gastrointestinal disorder NOS, Skin rash... AEs leading to discontinuation/dose reduction: Gastrointestinal disorder NOS (severe) Skin rash Reaction skin (serious) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf

AEs

AE	Significance	Dose	Population
Skin rash	Disc. AE	500 mg 1 times / day steady, oral Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf
Reaction skin	serious Disc. AE	500 mg 1 times / day steady, oral Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf
Gastrointestinal disorder NOS	severe Disc. AE	500 mg 1 times / day steady, oral Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT2B7 197 UGT1A9 148 UGT1A3 89 UGT1A1 246 OAT4 150 OAT3 747 OAT1 725 OAT2 153

Drug as perpetrator

Target	Modality	Activity
UGT1A3 99	inhibitor 4027 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250310001602757	no
UGT2B7 210	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17200831/ Page: 4.0	yes [IC50 0.3 uM]
OAT3 749	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 0.78 uM]
OAT1 730	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 0.83 uM]
OAT2 155	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 21.7 uM]
OAT4 150	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 61.7 uM]
UGT1A1 303	inhibitor 4027 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250310001602757	yes [Inhibition 25 uM]
UGT1A9 155	inhibitor 4027 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250310001602757	yes [Inhibition 25 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf Page: 2.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6717	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6717
ChemicalBook	CB5472051	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5472051
eMolecules	591932	https://www.emolecules.com/cgi-bin/more?vid=591932
MolPort	MolPort-001-839-968	https://www.molport.com/shop/molecule-link/MolPort-001-839-968
Selleck Chemicals	mefenamic-acid	http://www.selleckchem.com/products/mefenamic-acid.html
ZINC	ZINC000000020241	http://zinc15.docking.org/substances/ZINC000000020241

PubMed

Title	Date	PubMed
Case report: acute renal failure, thrombocytopenia and nonhemolytic icterus probably caused by mefenamic acid (Parkemed)-dependent antibodies.	1992	1284748
[A possible adverse effect from the association of losartan-mefenamic acid in hemodialysis].	2001	11385903
The first world report of botulinum A toxin injection for status migrainosus.	2001 Aug	11758858
Inhibition of store-operated calcium entry contributes to the anti-proliferative effect of non-steroidal anti-inflammatory drugs in human colon cancer cells.	2001 Jun 15	11351310
Acute renal failure from hemoglobinuric and interstitial nephritis secondary to iodine and mefenamic acid.	2001 Mar	11316248
Competition of tamoxifen with thyroxine for TBG binding: ligand binding assay and computational data.	2001 Nov	11849618
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Growth and hematological studies on Brazilian children of low socioeconomic level.	2001 Sep	11791475
[A case of nonsteroidal anti-inflammatory drugs (NSAIDs) induced colitis].	2001 Sep	11579497
Describing solubility of polymorphs in mixed solvents by CNIBS/R-K equation.	2002 Dec	12561255
Molecular modelling of the differential interaction between several non-steroidal anti-inflammatory drugs and human prostaglandin endoperoxide H synthase-2 (h-PGHS-2).	2002 Jan	11858641
Characterization of mefenamic acid-guaiacol ester: stability and transport across Caco-2 cell monolayers.	2002 Jul	12180533
Sulfation of R(-)-apomorphine in the human liver and duodenum, and its inhibition by mefenamic acid, salicylic acid and quercetin.	2002 Jul	12162854
Comparison of fennel and mefenamic acid for the treatment of primary dysmenorrhea.	2003 Feb	12566188
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
Benefits and risks of pharmacological agents used for the treatment of menorrhagia.	2004	14717620
Biological activity of five antibacterial flavonoids from Combretum erythrophyllum (Combretaceae).	2004 Aug	15234754
[Acute renal failure--"a well meant present from a friend"].	2004 Dec	15651168
Liquid chromatography method for determination of mefenamic acid in human serum.	2004 Feb 5	14698254
Tracking acidic pharmaceuticals, caffeine, and triclosan through the wastewater treatment process.	2005 Jan	15683164

Patents

Sample Use Guides

In Vivo Use Guide

For the relief of acute pain in adults and adolescents ≥14 years of age, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours as needed, usually not to exceed one week. For the treatment of primary dysmenorrhea, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours, given orally, starting with the onset of bleeding and associated symptoms. Clinical studies indicate that effective treatment can be initiated with the start of menses and should not be necessary for more than 2 to 3 days.

Route of Administration: Oral

In Vitro Use Guide

Mefenamic acid (0-100 uM) exerted cytotoxic effects on oral squamous cell carcinoma (KB), osteogenic sarcoma (Saos-2), and human brain astrocytoma (1321N) cells, where the viability was approximately 75%. Malignant gliomas (U-87MG) cells were resistant to mefenamic acid.

Name

Type

Language

GARDAN

Preferred Name

English

MEFENAMIC ACID

Official Name

English

M01AG01

Code

English

PONSTEL

Brand Name

English

N-2,3-Xylylanthranilic acid

Systematic Name

English

CI-473

Code

English

CN-35355

Code

English

MEFENAMATE

Common Name

English

MEFENAMIC ACID [EP MONOGRAPH]

Common Name

English

MEFENAMIC ACID [MART.]

Common Name

English

MEFENAMINIC ACID

Common Name

English

NSC-94437

Code

English

2-(2,3-DIMETHYLPHENYL)AMINOBENZOIC ACID

Systematic Name

English

BENZOIC ACID, 2-(2,3-DIMETHYLPHENYL)AMINO-

Common Name

English

MEFENAMIC ACID [VANDF]

Common Name

English

J2.344B

Code

English

MEFENAMIC ACID [MI]

Common Name

English

MEPHENAMIC ACID

Common Name

English

MEFENAMIC ACID [HSDB]

Common Name

English

MEFENAMIC ACID [USP MONOGRAPH]

Common Name

English

MEFENAMIC ACID [USAN]

Common Name

English

MEFENAMIC ACID [JAN]

Common Name

English

MEFENAMIC ACID [USP-RS]

Common Name

English

MEFENAMIC ACID [ORANGE BOOK]

Common Name

English

mefenamic acid [INN]

Common Name

English

Mefenamic acid [WHO-DD]

Common Name

English

INF-3355

Code

English

MEPHENAMINIC ACID

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000000160