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Identification
NameCarprofen
Accession NumberDB00821  (APRD00849)
TypeSmall Molecule
GroupsApproved, Withdrawn
Description

Carprofen is a non-steroidal anti-inflammatory drug (NSAID) that is used by veterinarians as a supportive treatment for the relief of arthritic symptoms in geriatric dogs. Carprofen was previously used in human medicine for over 10 years (1985-1995). It was generally well tolerated, with the majority of adverse effects being mild, such as gastro-intestinal pain and nausea, similar to those recorded with aspirin and other non-steroidal anti-inflammatory drugs. It is no longer marketed for human usage, after being withdrawn on commercial grounds. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
(+-)-6-chloro-alpha-Methylcarbazole-2-acetic acidNot AvailableNot Available
(+/-)-2-(3-chloro-9H-carbazol-7-yl)propanoic acidNot AvailableNot Available
2-(6-Chloro-9H-carbazol-2-yl)-propionic acidNot AvailableNot Available
6-chloro-alpha-Methyl-9H-carbazole-2-acetic acidNot AvailableNot Available
CarprofenGerman INN
CarprofèneFrenchINN
CarprofenoSpanishINN
CarprofenumLatinINN
SaltsNot Available
Brand names
NameCompany
lmadylRoche
lmafenRoche
RimadytRoche
Brand mixturesNot Available
Categories
CAS number53716-49-7
WeightAverage: 273.714
Monoisotopic: 273.05565634
Chemical FormulaC15H12ClNO2
InChI KeyPUXBGTOOZJQSKH-UHFFFAOYSA-N
InChI
InChI=1S/C15H12ClNO2/c1-8(15(18)19)9-2-4-11-12-7-10(16)3-5-13(12)17-14(11)6-9/h2-8,17H,1H3,(H,18,19)
IUPAC Name
2-(6-chloro-9H-carbazol-2-yl)propanoic acid
SMILES
CC(C(O)=O)C1=CC2=C(C=C1)C1=C(N2)C=CC(Cl)=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassCarbazoles
Direct parentCarbazoles
Alternative parentsPhenylpropanoic Acids; Indoles; Chlorobenzenes; Aryl Chlorides; Pyrroles; Polyamines; Enolates; Carboxylic Acids; Organochlorides
Substituents2-phenylpropanoic-acid; indole; chlorobenzene; benzene; aryl halide; aryl chloride; pyrrole; carboxylic acid derivative; polyamine; carboxylic acid; enolate; organohalogen; organonitrogen compound; organochloride
Classification descriptionThis compound belongs to the carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
Pharmacology
IndicationFor use as a pain reliever in the treatment of joint pain and post-surgical pain.
PharmacodynamicsCarprofen is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class that includes ibuprofen, naproxen, and ketoprofen. It is no longer used in the clinical setting, but is approved for use in dogs. Carprofen is non-narcotic and has characteristic analgesic and antipyretic activity approximately equipotent to indomethacin in animal models.
Mechanism of actionThe mechanism of action of carprofen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity. In an in vitro study using canine cell cultures, carprofen demonstrated selective inhibition of COX-2 versus COX-1.
AbsorptionRapidly and nearly completely absorbed (more than 90% bioavailable) when administered orally.
Volume of distributionNot Available
Protein bindingHigh (99%)
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeApproximately 8 hours (range 4.5–9.8 hours) in dogs.
ClearanceNot Available
ToxicitySymptoms of NSAID overdose include dizziness and nystagmus. Oral LD50 in mouse and rat is 282 mg/kg and 149 mg/kg, respectively.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Carprofen Action PathwayDrug actionSMP00694
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9742
Caco-2 permeable + 0.5595
P-glycoprotein substrate Non-substrate 0.7062
P-glycoprotein inhibitor I Non-inhibitor 0.985
P-glycoprotein inhibitor II Non-inhibitor 0.9319
Renal organic cation transporter Non-inhibitor 0.8485
CYP450 2C9 substrate Non-substrate 0.7405
CYP450 2D6 substrate Non-substrate 0.8318
CYP450 3A4 substrate Non-substrate 0.6389
CYP450 1A2 substrate Inhibitor 0.6573
CYP450 2C9 substrate Non-inhibitor 0.7193
CYP450 2D6 substrate Non-inhibitor 0.9481
CYP450 2C19 substrate Non-inhibitor 0.7037
CYP450 3A4 substrate Non-inhibitor 0.8308
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.794
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.8521
Biodegradation Not ready biodegradable 0.9874
Rat acute toxicity 3.4155 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9725
hERG inhibition (predictor II) Non-inhibitor 0.8697
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point195-199Berger, L. and Corraz, A.J.; US. Patent 3,896,145; July 22,1975; assigned to Hoffmann- LaRoche, Inc.
water solubilityPractically insoluble at 25 °CNot Available
logP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00379ALOGPS
logP4.09ALOGPS
logP3.88ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)4.42ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area53.09 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity74.16 m3·mol-1ChemAxon
Polarizability28.56 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Berger, L. and Corraz, A.J.; US. Patent 3,896,145; July 22,1975; assigned to Hoffmann-
LaRoche, Inc.

General ReferenceNot Available
External Links
ResourceLink
PubChem Compound2581
PubChem Substance46505357
ChemSpider2483
BindingDB50097346
ChEBI364453
ChEMBLCHEMBL1316
Therapeutic Targets DatabaseDAP000975
PharmGKBPA164781361
Drug Product Database2246557
WikipediaCarprofen
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(24.5 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Kay-Mugford P, Benn SJ, LaMarre J, Conlon P: In vitro effects of nonsteroidal anti-inflammatory drugs on cyclooxygenase activity in dogs. Am J Vet Res. 2000 Jul;61(7):802-10. Pubmed
  2. Brideau C, Van Staden C, Chan CC: In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats. Am J Vet Res. 2001 Nov;62(11):1755-60. 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. Beretta C, Garavaglia G, Cavalli M: COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res. 2005 Oct;52(4):302-6. Pubmed
  5. Narlawar R, Perez Revuelta BI, Haass C, Steiner H, Schmidt B, Baumann K: Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators. J Med Chem. 2006 Dec 28;49(26):7588-91. Pubmed
  6. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Beretta C, Garavaglia G, Cavalli M: COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res. 2005 Oct;52(4):302-6. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 02, 2014 14:44