You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameMeclofenamic acid
Accession NumberDB00939  (APRD01090)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis. [PubChem]

Structure
Thumb
Synonyms
Acide meclofenamique
Acido meclofenamico
Acidum meclofenamicum
CI-583
INF 4668
Meclofenamate
N-(2,6-Dichloro-3-methylphenyl)anthranilic acid
N-(2,6-Dichloro-m-tolyl)anthranilic acid
N-(3-Methyl-2,6-dichlorophenyl)anthranilic acid
External Identifiers
  • CI 583
  • Cl 583
  • INF 4668
Approved Prescription ProductsNot Available
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Meclofenamate Sodiumcapsule50 mg/1oralMylan Pharmaceuticals Inc.1986-09-03Not applicableUs
Meclofenamate Sodiumcapsule100 mg/1oralMylan Pharmaceuticals Inc.1986-09-03Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EthosYung Shin
EucomeU-Liang
MeclomenPfizer
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Meclofenamate sodium
ThumbNot applicableDBSALT001241
Categories
UNII48I5LU4ZWD
CAS number644-62-2
WeightAverage: 296.149
Monoisotopic: 295.016684015
Chemical FormulaC14H11Cl2NO2
InChI KeyInChIKey=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)
IUPAC Name
2-[(2,6-dichloro-3-methylphenyl)amino]benzoic acid
SMILES
CC1=C(Cl)C(NC2=CC=CC=C2C(O)=O)=C(Cl)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminobenzoic acids. These are benzoic acids containing an amine group attached to the benzene moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentAminobenzoic acids
Alternative Parents
Substituents
  • Aminobenzoic acid
  • Benzoic acid
  • Aminotoluene
  • Substituted aniline
  • 1,3-dichlorobenzene
  • Benzoyl
  • Toluene
  • Halobenzene
  • Chlorobenzene
  • Aniline
  • Aryl halide
  • Aryl chloride
  • Vinylogous amide
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsMeclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals.
Mechanism of actionThe 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.
Related Articles
AbsorptionRapidly 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 bindingGreater 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 eliminationOther 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 lifeIn 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
ToxicityAfter 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9393
Blood Brain Barrier+0.8668
Caco-2 permeable+0.8398
P-glycoprotein substrateNon-substrate0.806
P-glycoprotein inhibitor INon-inhibitor0.8943
P-glycoprotein inhibitor IINon-inhibitor0.9474
Renal organic cation transporterNon-inhibitor0.9094
CYP450 2C9 substrateNon-substrate0.6402
CYP450 2D6 substrateNon-substrate0.9164
CYP450 3A4 substrateNon-substrate0.6566
CYP450 1A2 substrateInhibitor0.9236
CYP450 2C9 inhibitorInhibitor0.9106
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.8271
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.558
Ames testNon AMES toxic0.8633
CarcinogenicityNon-carcinogens0.5329
BiodegradationNot ready biodegradable0.9709
Rat acute toxicity3.0345 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9502
hERG inhibition (predictor II)Non-inhibitor0.872
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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
FormRouteStrength
Capsuleoral100 mg/1
Capsuleoral50 mg/1
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point248-250U.S. Patent 3,313,848.
water solubility30 mg/LMERCK INDEX (1996)
logP5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00366 mg/mLALOGPS
logP5.11ALOGPS
logP6.09ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)3.79ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area49.33 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity76.45 m3·mol-1ChemAxon
Polarizability28.44 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

U.S. Patent 3,313,848.

General ReferencesNot Available
External Links
ATC CodesM01AG04M02AA18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (74.2 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
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:12225961 ]
  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:11094641 ]
  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:15198222 ]
  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:10639181 ]
  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:8454631 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
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:10639181 ]
  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:12409963 ]
  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:15198222 ]
  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:16290292 ]
  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:7825862 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Iron ion binding
Specific Function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular Weight:
77982.595 Da
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:1539679 ]
  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:3020588 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic in...
Gene Name:
KCNQ2
Uniprot ID:
O43526
Molecular Weight:
95846.575 Da
References
  1. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. [PubMed:15598972 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other
General Function:
Voltage-gated potassium channel activity
Specific Function:
Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to sy...
Gene Name:
KCNQ3
Uniprot ID:
O43525
Molecular Weight:
96741.515 Da
References
  1. Peretz A, Degani N, Nachman R, Uziyel Y, Gibor G, Shabat D, Attali B: Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol. 2005 Apr;67(4):1053-66. Epub 2004 Dec 14. [PubMed:15598972 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
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:10220563 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Thyroid hormone transmembrane transporter activity
Specific Function:
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. May play a signifiant role in regulating T4 flux into and out of the brain (By similarity).
Gene Name:
SLCO1C1
Uniprot ID:
Q9NYB5
Molecular Weight:
78695.625 Da
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. doi: 10.1210/en.2008-0188. Epub 2008 Oct 9. [PubMed:18845642 ]
  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:10592235 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23