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Identification
Name Phenylbutazone
Accession Number DB00812 (APRD00409, DB08343)
Type small molecule
Groups approved
Description

A drug that has anti-inflammatory, antipyretic, and analgesic activities. It is especially effective in the treatment of ankylosing spondylitis. It also is useful in rheumatoid arthritis and Reiter's syndrome (investigational indication). Although phenylbutazone is effective in gouty arthritis, risk/benefit considerations indicate that this drug should not be employed for this disease. (From AMA Drug Evaluations Annual, 1994, p1822)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
'Esteve'
Alindor
Alka Butazolidin
Alkabutazona
Alqoverin
Anerval
Anpuzone
Antadol
Anuspiramin
Apo-Phenylbutazone
Arthrizon
Artizin
Artrizin
Artrizone
Artropan
Azdid
Azobutyl
Azolid
B.T.Z.
Benzone
Betazed
Bizolin
Bizolin 200
Bunetzone
Busone
Buta Phen
Butacompren
Butacote
Butadion
Butadiona
Butadione
Butagesic
Butalgina
Butalidon
Butaluy
Butapirazol
Butapirazole
Butapyrazole
Butarecbon
Butartril
Butartrina
Butatron
Butazina
Butazolidin
Butazolidine
Butazona
Bute
Butidiona
Butiwas-Simple
Butone
Butoz
Butylpyrin
Buvetzone
Buzon
Chembutazone
Cotylbutazone
Digibutina
Diossidone
Diozol
Diphebuzol
Diphenylbutazone
Ecobutazone
Elmedal
Equi Bute
Equipalazone
Eributazone
Exrheudon N
Febuzina
Fenartil
Fenibutal
Fenibutasan
Fenibutazona
Fenibutol
Fenilbutazona
Fenilbutina
Fenilbutine
Fenilidina
Fenotone
Fenylbutazon
Ia-But
Intalbut
Intrabutazone
Intrazone
Ipsoflame
Kadol
Lingel
Malgesic
Mepha-Butazon
Mephabutazon
Mephabutazone
Merizone
Nadazone
Nadozone
Neo-Zoline
Novophenyl
Phebuzin
Phebuzine
Phenbutazol
Phenbutazone
Phenopyrine
Phenyl-Mobuzon
Phenylbutaz
Phenylbutazonum
Phenyzene
Phenyzone
Pirarreumol "B"
Pirarreumol B
Praecirheumin
Pyrabutol
Pyrazolidin
Rectofasa
Reudo
Reudox
Reumasyl
Reumazin
Reumazol
Reumune
Reumuzol
Reupolar
Robizon-V
Robizone
Robizone-V
Rubatone
Scanbutazone
Schemergin
Shigrodin
Tazone
Tencodyne
Tetnor
Tevcodyne
Therazone
Ticinil
Todalgil
Usaf Ge-15
Uzone
VAC-10
Wescozone
Zolaphen
Zolidinum
First Prev Next Last
Brand mixtures
Brand Name Ingredients
Alka Phenyl Tab Aluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Alka Phenylbutazone Tab Aluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Phenylone Plus Tab Aluminum Hydroxide + Magnesium Trisilicate + Phenylbutazone
Categories
  • Anti-inflammatory Agents
  • Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number 50-33-9
Weight Average: 308.3743
Monoisotopic: 308.152477894
Chemical Formula C19H20N2O2
InChI Key InChIKey=VYMDGNCVAMGZFE-UHFFFAOYSA-N
InChI
InChI=1S/C19H20N2O2/c1-2-3-14-17-18(22)20(15-10-6-4-7-11-15)21(19(17)23)16-12-8-5-9-13-16/h4-13,17H,2-3,14H2,1H3
Plain Text
IUPAC Name
4-butyl-1,2-diphenylpyrazolidine-3,5-dione
SMILES
CCCCC1C(=O)N(N(C1=O)C1=CC=CC=C1)C1=CC=CC=C1
Plain Text
Mass Spec show (9.03 KB)
Taxonomy
Kingdom Organic
Classes
  • Phenylhydrazines
  • Anilines
Substructures
  • Pyrazolones
  • Amino Ketones
  • Benzene and Derivatives
  • Pyrazolidines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Hydrazine Derivatives
  • Phenylhydrazines
  • Anilines
Pharmacology
Indication For the treatment of backache and ankylosing spondylitis
Pharmacodynamics Phenylbutazone is a synthetic, pyrazolone derivative. It is a nonhormonal anti-inflammatory, antipyretic compound useful in the management of inflammatory conditions. The apparent analgesic effect is probably related mainly to the compound's anti-inflammatory properties and arise from its ability to reduce production of prostaglandin H and prostacyclin. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostacylcin causes vascular constriction platelet disaggregation
Mechanism of action Phenylbutazone binds to and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide (H2O2) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Oral, LD50 = 238 mg/kg (mouse); Oral, LD50 = 781 mg/kg (rabbit); Oral, LD50 = 245 mg/kg (rat); Oral, LD50 = 375 mg/kg (rat)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Novartis pharmaceuticals corp
  • Ivax pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Phenylbutazone powder 1.16 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 105 °C PhysProp
water solubility 47.5 mg/L (at 30 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 3.16 SANGSTER (1994)
logS -3.81 ADME Research, USCD
pKa 4.5 SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
Property Value Source
water solubility 1.44e-01 g/l ALOGPS
logP 2.81 ALOGPS
logP 4.14 ChemAxon
logS -3.3 ALOGPS
pKa (strongest acidic) 5.13 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 40.62 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 88.76 ChemAxon
polarizability 34.15 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00510 Link_out
KEGG Compound C07440 Link_out
PubChem Compound 4781 Link_out
PubChem Substance 46507038 Link_out
ChemSpider 4617 Link_out
ChEBI 48574 Link_out
ChEMBL 48574 Link_out
Therapeutic Targets Database DAP000974 Link_out
PharmGKB PA450932 Link_out
HET P1Z Link_out
Drug Product Database 596701 Link_out
Wikipedia http://en.wikipedia.org/wiki/Phenylbutazone Link_out
ATC Codes
  • M01AA01
  • M02AA01
AHFS Codes
  • 28:08.04.92
PDB Entries Not Available
FDA label Not Available
MSDS show (73.1 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol The NSAID, phenylbutazone, may increase the anticoagulant effect of acenocoumarol.
Acetohexamide Phenylbutazone may increase the effect of acetohexamide.
Anisindione The NSAID, phenylbutazone, may increase the anticoagulant effect of anisindione.
Chlorpropamide Phenylbutazone increases the effect of the hypoglycemic agent
Dicumarol The NSAID, phenylbutazone, may increase the anticoagulant effect of dicumarol.
Ethotoin The NSAID, phenylbutazone, may increase the hydantoin effect of ethotoin.
Fosphenytoin The NSAID, phenylbutazone, may increase the hydantoin effect of fosphenytoin.
Gliclazide Phenylbutazone increases the effect of the hypoglycemic agent
Glipizide Phenylbutazone increases the effect of the hypoglycemic agent
Glisoxepide Phenylbutazone increases the effect of the hypoglycemic agent
Glyburide Phenylbutazone increases the effect of the hypoglycemic agent
Glycodiazine Phenylbutazone increases the effect of the hypoglycemic agent
Lithium The NSAID, phenylbutazone, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Mephenytoin The NSAID, phenylbutazone, may increase the hydantoin effect of mephenytoin.
Methotrexate The NSAID, phenylbutazone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Phenytoin The NSAID, phenylbutazone, may increase the therapeutic and adverse effects of phenytoin.
Tolazamide Phenylbutazone increases the effect of the hypoglycemic agent
Tolbutamide Phenylbutazone increases the effect of the hypoglycemic agent
Warfarin The NSAID, phenylbutazone, may increase the anticoagulant effect of warfarin.
Food Interactions
  • Take with food to reduce irritation. Avoid alcohol.
Targets

1. 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. Arifah AK, Lees P: Pharmacodynamics and pharmacokinetics of phenylbutazone in calves. J Vet Pharmacol Ther. 2002 Aug;25(4):299-309. Pubmed
  2. Takada Y, Bhardwaj A, Potdar P, Aggarwal BB: Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004 Dec 9;23(57):9247-58. Pubmed
  3. 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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostacyclin synthase

Pharmacological action: yes
Actions: inhibitor

Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2)

Organism class: human
UniProt ID: Q16647 Link_out
Gene: PTGIS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Reed GA, Griffin IO, Eling TE: Inactivation of prostaglandin H synthase and prostacyclin synthase by phenylbutazone. Requirement for peroxidative metabolism. Mol Pharmacol. 1985 Jan;27(1):109-14. Pubmed
  4. Marnett LJ, Siedlik PH, Ochs RC, Pagels WR, Das M, Honn KV, Warnock RH, Tainer BE, Eling TE: Mechanism of the stimulation of prostaglandin H synthase and prostacyclin synthase by the antithrombotic and antimetastatic agent, nafazatrom. Mol Pharmacol. 1984 Sep;26(2):328-35. Pubmed
  5. Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P: Phenylbutazone in the horse: a review. J Vet Pharmacol Ther. 1986 Mar;9(1):1-25. Pubmed

3. 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. Zitova A, Hynes J, Kollar J, Borisov SM, Klimant I, Papkovsky DB: Analysis of activity and inhibition of oxygen-dependent enzymes by optical respirometry on the LightCycler system. Anal Biochem. 2010 Feb 15;397(2):144-51. Epub 2009 Oct 20. Pubmed
  2. 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
  3. Morton AJ, Campbell NB, Gayle JM, Redding WR, Blikslager AT: Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis. Res Vet Sci. 2005 Apr;78(2):189-92. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. 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. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  2. Uwai Y, Saito H, Inui K: Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur J Pharmacol. 2000 Dec 1;409(1):31-6. Pubmed
  3. 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 family 22 member 8

Actions: inhibitor

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed

3. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19