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Identification
NameCarprofen
Accession NumberDB00821  (APRD00849)
TypeSmall Molecule
GroupsApproved, Vet Approved, Withdrawn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 It is no longer marketed for human usage, after being withdrawn on commercial grounds.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
(+-)-6-chloro-alpha-Methylcarbazole-2-acetic acid
(+/-)-2-(3-chloro-9H-carbazol-7-yl)propanoic acid
2-(6-Chloro-9H-carbazol-2-yl)-propionic acid
6-chloro-alpha-Methyl-9H-carbazole-2-acetic acid
Carprofen
Carprofène
Carprofeno
Carprofenum
External Identifiers
  • C 5720
  • C 8012
  • Ro 20-5720/000
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
lmadylRoche
lmafenRoche
RimadytRoche
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIFFL0D546HO
CAS number53716-49-7
WeightAverage: 273.714
Monoisotopic: 273.05565634
Chemical FormulaC15H12ClNO2
InChI KeyInChIKey=PUXBGTOOZJQSKH-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassCarbazoles
Direct ParentCarbazoles
Alternative Parents
Substituents
  • Carbazole
  • Indole
  • Chlorobenzene
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Pyrrole
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9742
Caco-2 permeable+0.5595
P-glycoprotein substrateNon-substrate0.7062
P-glycoprotein inhibitor INon-inhibitor0.985
P-glycoprotein inhibitor IINon-inhibitor0.9319
Renal organic cation transporterNon-inhibitor0.8485
CYP450 2C9 substrateNon-substrate0.7405
CYP450 2D6 substrateNon-substrate0.8318
CYP450 3A4 substrateNon-substrate0.6389
CYP450 1A2 substrateInhibitor0.6573
CYP450 2C9 inhibitorNon-inhibitor0.7193
CYP450 2D6 inhibitorNon-inhibitor0.9481
CYP450 2C19 inhibitorNon-inhibitor0.7037
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.794
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8521
BiodegradationNot ready biodegradable0.9874
Rat acute toxicity3.4155 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9725
hERG inhibition (predictor II)Non-inhibitor0.8697
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
Packagers
Dosage formsNot Available
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 Solubility0.00379 mg/mLALOGPS
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 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

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

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (24.5 KB)
Interactions
Drug Interactions
Drug
PorfimerCarprofen may increase the photosensitizing activities of Porfimer.
VerteporfinCarprofen may increase the photosensitizing activities of Verteporfin.
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. 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. 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:10895904 ]
  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:11703020 ]
  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. 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:15939622 ]
  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:17181139 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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. 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:15939622 ]

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. 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:9880528 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23