Banner
targets (3) transporters (2)
for drugs
Identification
Name Meclofenamic acid
Accession Number DB00939 (APRD01090)
Type small molecule
Groups approved
Description

A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Acide meclofenamique [INN-French]
  • Acido meclofenamico [INN-Spanish]
  • Acidum meclofenamicum [INN-Latin]
  • Meclofenamate
  • Meclomen (free acid)
  • Meclophenamic acid
Brand names
  • Arquel
Brand name mixtures Not Available
Categories
  • Cyclooxygenase Inhibitors
CAS number 644-62-2
Weight Average: 296.149
Monoisotopic: 295.016684015
Chemical Formula C14H11Cl2NO2
InChI Key InChIKey=SBDNJUWAMKYJOX-UHFFFAOYSA-N
InChI
InChI=1S/C14H11Cl2NO2/c1-8-6-7-10(15)13(12(8)16)17-11-5-3-2-4-9(11)14(18)19/h2-7,17H,1H3,(H,18,19)
Plain Text
IUPAC Name
2-[(2,6-dichloro-3-methylphenyl)amino]benzoic acid
SMILES
CC1=CC=C(Cl)C(NC2=C(C=CC=C2)C(O)=O)=C1Cl
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
  • Aryl Halides
  • Halobenzenes
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Benzoyl Derivatives
  • Anilines
Pharmacology
Indication For the relief of mild to moderate pain, for the treatment of primary dysmenorrhea and for the treatment of idiopathic heavy menstrual blood loss. Also for relief of the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis.
Pharmacodynamics Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals.
Mechanism of action The mode of action, like that of other nonsteroidal anti-inflammatory agents, is not known. Therapeutic action does not result from pituitary-adrenal stimulation. In animal studies, meclofenamic acid was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site. In vitro meclofenamic acid was found to be an inhibitor of human leukocyte 5-lipoxygenase activity. These properties may be responsible for the anti-inflammatory action of meclofenamic acid. There is no evidence that meclofenamic acid alters the course of the underlying disease.
Absorption Rapidly absorbed in man following single and multiple oral doses with peak plasma concentrations occurring in 0.5 to 2 hours. The concomitant administration of antacids (aluminum and magnesium hydroxides) does not interfere with absorption of meclofenamic acid. Unlike most NSAIDs, which when administered with food have a decrease in rate but not in extent of absorption, meclofenamic acid is decreased in both. It has been reported that following the administration of meclofenamic acid capsules one-half hour after a meal, the average extent of bioavailability decreased by 26%, the average peak concentration (Cmax) decreased fourfold and the time to Cmax was delayed by 3 hours.
Volume of distribution
  • 9.1 to 43.2 L
Protein binding Greater than 99% bound to plasma proteins over a wide drug concentration range.
Metabolism

Hepatic. Meclofenamic acid is extensively metabolized to an active metabolite (Metabolite I; 3-hydroxymethyl metabolite of meclofenamic acid) and at least six other less well characterized minor metabolites. Only Metabolite I has been shown in vitro to inhibit cyclooxygenase activity with approximately one fifth the activity of meclofenamic acid.
Route of elimination Other metabolites, whose excretion rates are unknown, account for the remaining 35% to 62% of the dose excreted in the urine. The remainder of the administered dose (approximately 30%) is eliminated in the feces (apparently through biliary excretion). Trace amounts of meclofenamate sodium are excreted in human breast milk.
Half life In a study in 10 healthy subjects following a single oral dose the apparent elimination half-life ranged from 0.8 to 5.3 hours. Metabolite I (3-hydroxymethyl metabolite of meclofenamic acid) has a mean half-life of approximately 15 hours.
Clearance
  • Oral cl=206 mL/min
Toxicity After a massive overdose, CNS stimulation may be manifested by irrational behavior, marked agitation and generalized seizures. Following this phase, renal toxicity (falling urine output, rising creatinine, abnormal urinary cellular elements) may be noted with possible oliguria or anuria and azotemia. A 24 year-old male was anuric for approximately one week after ingesting an overdose of 6 to 7 grams of meclofenamate sodium. Spontaneous diuresis and recovery subsequently occurred.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Quantum pharmics ltd
  • American therapeutics inc
  • Barr laboratories inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Sandoz inc
  • Usl pharma inc
  • Vitarine pharmaceuticals inc
  • Watson laboratories inc
  • Parke davis div warner lambert co
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 257 oC
Experimental Properties
Property Value Source
water solubility 30 mg/L PhysProp
logP 5 PhysProp
Predicted Properties
Property Value Source
water solubility 3.66e-03 g/l ALOGPS
logP 5.11 ALOGPS
logP 6.09 ChemAxon Molconvert
logS -4.91 ALOGPS
pKa 17.05 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 76.45 ChemAxon Molconvert
polarizability 28.44 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02341 Link_out
KEGG Compound C02996 Link_out
PubChem Compound 4037 Link_out
PubChem Substance 46507887 Link_out
ChemSpider 3897 Link_out
BindingDB 22971 Link_out
Therapeutic Targets Database DNC000919 Link_out
PharmGKB PA450341 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/meclofen.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Meclofenamic_acid Link_out
ATC Codes
  • M01AG04
  • M02AA18
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (74.2 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Prostaglandin G/H synthase 1

Pharmacological action: yes
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. Perez-Vizcaino F, Lopez-Lopez JG, Santiago R, Cogolludo A, Zaragoza-Arnaez F, Moreno L, Alonso MJ, Salaices M, Tamargo J: Postnatal maturation in nitric oxide-induced pulmonary artery relaxation involving cyclooxygenase-1 activity. Am J Physiol Lung Cell Mol Physiol. 2002 Oct;283(4):L839-48. Pubmed
  2. Shiels IA, Whitehouse MW: Lyprinol: anti-inflammatory and uterine-relaxant activities in rats, with special reference to a model for dysmenorrhoea. Allerg Immunol (Paris). 2000 Sep;32(7):279-83. Pubmed
  3. Wilson JE, Chandrasekharan NV, Westover KD, Eager KB, Simmons DL: Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs. Am J Vet Res. 2004 Jun;65(6):810-8. Pubmed
  4. Kalgutkar AS, Crews BC, Rowlinson SW, Marnett AB, Kozak KR, Remmel RP, Marnett LJ: Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):925-30. Pubmed
  5. Meade EA, Smith WL, DeWitt DL: Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1993 Mar 25;268(9):6610-4. Pubmed

2. 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. Kalgutkar AS, Crews BC, Rowlinson SW, Marnett AB, Kozak KR, Remmel RP, Marnett LJ: Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):925-30. Pubmed
  2. Traupe T, Lang M, Goettsch W, Munter K, Morawietz H, Vetter W, Barton M: Obesity increases prostanoid-mediated vasoconstriction and vascular thromboxane receptor gene expression. J Hypertens. 2002 Nov;20(11):2239-45. Pubmed
  3. Wilson JE, Chandrasekharan NV, Westover KD, Eager KB, Simmons DL: Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs. Am J Vet Res. 2004 Jun;65(6):810-8. Pubmed
  4. Narsinghani T, Chaturvedi SC: QSAR analysis of meclofenamic acid analogues as selective COX-2 inhibitors. Bioorg Med Chem Lett. 2006 Jan 15;16(2):461-8. Epub 2005 Nov 14. Pubmed
  5. Smith WL, Meade EA, DeWitt DL: Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. Ann N Y Acad Sci. 1994 Nov 15;744:50-7. Pubmed

3. Arachidonate 5-lipoxygenase

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: P09917 Link_out
Gene: ALOX5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yu XY, Hubbard W, Spannhake EW: Inhibition of canine tracheal smooth muscle by mediators from cultured bronchial epithelial cells. Am J Physiol. 1992 Feb;262(2 Pt 1):L229-34. Pubmed
  2. Boctor AM, Eickholt M, Pugsley TA: Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro. Prostaglandins Leukot Med. 1986 Aug;23(2-3):229-38. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. Pubmed

2. Solute carrier organic anion transporter family member 1C1

Actions: inhibitor

Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol, estrone-3-sulfate and sulfobromophthalein (BSP) are transported with much lower efficiency

UniProt ID: Q9NYB5 Link_out
Gene: SLCO1C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. Epub 2008 Oct 9. Pubmed
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:44

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.