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=CC=CC(NC2=CC=CC=C2C(O)=O)=C1C

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-2 191 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9626023	Inhibitor 8146		2.9 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 607 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	Palliative		Approved 8307	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 3.78691191E11
Primary dysmenorrhea 14 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/015034s044lbl.pdf	Palliative		Approved 8307	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 3.78691191E11

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 (starting) 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 (starting) 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 (starting) 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 (starting) 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 985

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT2B7 145 UGT1A9 115 UGT1A3 84 UGT1A1 200 OAT4 145 OAT3 625 OAT1 584 OAT2 144

Drug as perpetrator

Target	Modality	Activity
UGT1A3 93	inhibitor 3185 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250310001602757	no
UGT2B7 156	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17200831/ Page: 4.0	yes [IC50 0.3 uM]
OAT3 627	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 0.78 uM]
OAT1 588	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 0.83 uM]
OAT2 146	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 21.7 uM]
OAT4 145	inhibitor 3185 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes [IC50 61.7 uM]
UGT1A1 249	inhibitor 3185 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250310001602757	yes [Inhibition 25 uM]
UGT1A9 120	inhibitor 3185 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250310001602757	yes [Inhibition 25 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C9 985	substrate 3264 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
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
eMolecules	591932	https://www.emolecules.com/cgi-bin/more?vid=591932

PubMed

Title	Date	PubMed
Case report: acute renal failure, thrombocytopenia and nonhemolytic icterus probably caused by mefenamic acid (Parkemed)-dependent antibodies.	1992	1284748
Crystal structure of the inclusion complex of beta-cyclodextrin with mefenamic acid from high-resolution synchrotron powder-diffraction data in combination with molecular-mechanics calculations.	2002 Dec	12456984
Renal papillary necrosis.	2002 Nov-Dec	12512867
The enhancing effect of a triethanolamine-ethanol-isopropyl myristate mixed system on the skin permeation of acidic drugs.	2002 Oct	12392091
Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants.	2003	12917997
Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants.	2003	12804505
Ibuprofen for the treatment of a patent ductus arteriosus in preterm and/or low birth weight infants.	2003	12804469
Demographics, assessment and management of pain in the elderly.	2003	12513114
Mefenamate, an agent that fails to attenuate experimental cerebral infarction.	2003 Aug	12945952
The use of complexation with alkanolamines to facilitate skin permeation of mefenamic acid.	2003 Aug 27	12927383
Effects of anti-inflammatory drugs on convulsant activity of quinolones: a comparative study of drug interaction between quinolones and anti-inflammatory drugs.	2003 Dec	14691652
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
Green tea catechins evoke a phasic contraction in rat aorta via H2O2-mediated multiple-signalling pathways.	2003 Jan-Feb	12542460
[Variance of bioavailability of pharmaceutical preparations and analysis of factors affecting it].	2003 Jul	12875233
Vasopressin mediates neuroprotection in mice by stimulation of V1 vasopressin receptors: influence of PI-3 kinase and gap junction inhibitors.	2003 Jun	15266902
Comprehensive study of the luminescent properties and lifetimes of Eu(3+) and Tb(3+) chelated with various ligands in aqueous solutions: influence of the synergic agent, the surfactant and the energy level of the ligand triplet.	2003 Jun	12736069
Inactivation of creatine kinase during the interaction of mefenamic acid with horseradish peroxidase and hydrogen peroxide: participation by the mefenamic acid radical.	2003 Mar 14	12597989
Menorrhagia: an update.	2003 May	12752071
Investigations on mefenamic acid sustained release tablets with water-insoluble gel.	2003 May	12729834
Salicylate induces tinnitus through activation of cochlear NMDA receptors.	2003 May 1	12736364
Effectiveness and mechanism of action of desmopressin in the treatment of copper intrauterine device-related menorrhagia: a pilot study.	2003 Nov	14585881
Interaction between nitric oxide and prostanoids in arterioles of rat cremaster muscle in vivo.	2003 Sep	12730058
[Effect of acetylsalicylic and mefenamic acids on cytoarchitectonic of skin in rats with acute local cryogenic trauma].	2003 Sep-Oct	14650215
Peritoneal dialysis solutions contract arteries through endothelium-independent prostanoid pathways.	2004	15384822
Determination of nonsteroidal anti-inflammatory drugs, caffeine, and triclosan in wastewater by gas chromatography-mass spectrometry.	2004	15332662
Benefits and risks of pharmacological agents used for the treatment of menorrhagia.	2004	14717620
Solid-state characterization of mefenamic acid.	2004 Apr	14999737
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
The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.	2004 Feb	15032311
Liquid chromatography method for determination of mefenamic acid in human serum.	2004 Feb 5	14698254
Double-blind study to evaluate efficacy and safety of meloxicam 7.5 mg and 15 mg versus mefenamic acid 1500 mg in the treatment of primary dysmenorrhea.	2004 Jul	15225193
The use of recombinant human epidermal growth factor (rhEGF) in a gentleman with drug-induced Steven Johnson syndrome.	2004 Jul 15	15347507
Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation.	2004 Jul 2	15117964
Rapid ESI-MS method for examining the thermal decomposition of pharmaceuticals.	2004 Jun	15124212
Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine.	2004 Jun 28	15222892
The emulsification and solubilisation properties of polyglycolysed oils in self-emulsifying formulations.	2004 Mar	15025855
Salicylidene salicylhydrazide, a selective inhibitor of beta 1-containing GABAA receptors.	2004 May	15100159
Evaluation of the bioactivity of triterpene mixture isolated from Carmona retusa (Vahl.) Masam leaves.	2004 May	15099847
Factors associated with iron deficiency anemia in Brazilian preschool children.	2004 May-Jun	15192767
Liver injury induced by the non-steroidal anti-inflammatory drug mefenamic acid.	2004 Nov	15510325
Compounds exhibiting selective efficacy for different beta subunits of human recombinant gamma-aminobutyric acid A receptors.	2004 Nov	15210837
Effect of mefenamic acid on controlling irregular uterine bleeding in DMPA users.	2004 Oct	15451330
Mefenamic acid-induced apoptosis in human liver cancer cell-lines through caspase-3 pathway.	2004 Oct 1	15350819
Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom.	2004 Oct 15	15364527
Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: a review of the literature.	2004 Sep	15487807
The occurrence of selected human pharmaceutical compounds in UK estuaries.	2004 Sep	15325211
Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents.	2005 Apr	15451637
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

MEFENAMIC ACID

Official Name

English

GARDAN

Brand 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