Identification

Name
Carprofen
Accession Number
DB00821  (APRD00849)
Type
Small Molecule
Groups
Approved, Vet approved, Withdrawn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 It is no longer marketed for human usage, after being withdrawn on commercial grounds.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 IDs
C 5720 / C 8012 / Ro 20-5720/000
International/Other Brands
lmadyl (Roche) / lmafen (Roche) / Rimadyt (Roche)
Categories
UNII
FFL0D546HO
CAS number
53716-49-7
Weight
Average: 273.714
Monoisotopic: 273.05565634
Chemical Formula
C15H12ClNO2
InChI Key
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

Pharmacology

Indication

For use as a pain reliever in the treatment of joint pain and post-surgical pain.

Pharmacodynamics

Carprofen 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 action

The 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.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
UProstaglandin G/H synthase 1
inhibitor
Human
Absorption

Rapidly and nearly completely absorbed (more than 90% bioavailable) when administered orally.

Volume of distribution
Not Available
Protein binding

High (99%)

Metabolism

Hepatic.

Route of elimination
Not Available
Half life

Approximately 8 hours (range 4.5–9.8 hours) in dogs.

Clearance
Not Available
Toxicity

Symptoms 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
PathwayCategory
Carprofen Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of gastrointestinal bleeding can be increased when Carprofen is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of gastrointestinal bleeding can be increased when Carprofen is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Carprofen is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
4-hydroxycoumarinThe risk or severity of gastrointestinal bleeding can be increased when Carprofen is combined with 4-hydroxycoumarin.
AbacavirCarprofen may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Carprofen is combined with Abciximab.
AcarboseCarprofen may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololCarprofen may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Carprofen is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Carprofen is combined with Acemetacin.
Food Interactions
Not Available

References

Synthesis Reference

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

General References
Not Available
External Links
Human Metabolome Database
HMDB0014959
KEGG Compound
C18364
PubChem Compound
2581
PubChem Substance
46505357
ChemSpider
2483
BindingDB
50097346
ChEBI
364453
ChEMBL
CHEMBL1316
Therapeutic Targets Database
DAP000975
PharmGKB
PA164781361
Wikipedia
Carprofen
MSDS
Download (24.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
Packagers
  • Emcure Pharmaceuticals Ltd.
  • Norbrook Laboratories Ltd.
  • Vericore Ltd.
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)195-199Berger, 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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-2910000000-d2961d6d33669b09ac4d

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Carbazoles
Alternative Parents
Indoles / Benzenoids / Aryl chlorides / Pyrroles / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 4 more
Substituents
Carbazole / Indole / Aryl chloride / Aryl halide / Benzenoid / Pyrrole / Heteroaromatic compound / Carboxylic acid derivative / Carboxylic acid / Monocarboxylic acid or derivatives
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, carbazoles (CHEBI:364453)

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...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
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 gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
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 ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:50