DrugBank: Tenoxicam (DB00469)

targets (2) enzymes (1) transporters (1)

Identification

Name

Tenoxicam

Accession Number

DB00469 (APRD00011)

Type

small molecule

Groups

approved

Description

Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Tenoxicamum [INN-Latin]

Brand names

Apo-Tenoxicam
Novo-Tenoxicam
Tilcotil

Brand name mixtures

Not Available

Categories

Cyclooxygenase Inhibitors

CAS number

59804-37-4

Weight

Average: 337.374
Monoisotopic: 337.019097235

Chemical Formula

C₁₃H₁₁N₃O₄S₂

InChI Key

InChIKey=WZWYJBNHTWCXIM-RAXLEYEMSA-N

InChI

InChI=1S/C13H11N3O4S2/c1-16-10(13(18)15-9-4-2-3-6-14-9)11(17)12-8(5-7-21-12)22(16,19)20/h2-7,18H,1H3,(H,14,15)/b13-10-

Plain Text

IUPAC Name

(3Z)-3-{hydroxy[(pyridin-2-yl)amino]methylidene}-2-methyl-2H,3H,4H-1$l^{6},5,2-thieno[2,3-e][1$l^{6},2]thiazine-1,1,4-trione

SMILES

CN1S(=O)(=O)C2=C(SC=C2)C(=O)\C1=C(\O)NC1=NC=CC=C1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Pyridines and Derivatives
Aminopyridines and Derivatives

Substructures

Hydroxy Compounds
Amino Ketones
Pyridines and Derivatives
Sulfonyls
Aminopyridines and Derivatives
Heterocyclic compounds
Aromatic compounds
Sulfonamides
Thiophenes
Ketones

Pharmacology

Indication

For the treatment of rheumatoid arthritis, osteoarthritis, backache, and pain.

Pharmacodynamics

Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.

Mechanism of action

The antiinflammatory effects of tenoxicam may result from the inhibition of the enzyme cycooxygenase and the subsequent peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, their inhibition accounts for the peripheral analgesic effects of tenoxicam. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.

Absorption

Oral absorption of tenoxicam is rapid and complete (absolute bioavailability 100%).

Volume of distribution

Not Available

Protein binding

99%

Metabolism

Tenoxicam is metabolized in the liver to several pharmacologically inactive metabolites (mainly 5'-hydroxy-tenoxicam).

Enzyme	Metabolite	Reaction	K_m	V_max
Cytochrome P450 2C9	5'-Hydroxylornoxicam	5'-hydroxylation
Cytochrome P450 2C9	5'-hydroxytenoxicam	5'-hydroxylation	40	0

Route of elimination

Not Available

Half life

72 hours (range 59 to 74 hours)

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Tablet	Oral

Prices

Unit description	Cost	Unit
Apo-Tenoxicam 20 mg Tablet	1.21 USD	tablet

Patents

Not Available

Properties

State

solid

Melting point

211 oC

Experimental Properties

Property	Value	Source
water solubility	14.1 mg/L	PhysProp
logP	1.9	PhysProp

Predicted Properties

Property	Value	Source
water solubility	2.77e-01 g/l	ALOGPS
logP	1.82	ALOGPS
logP	1.22	ChemAxon Molconvert
logS	-3.09	ALOGPS
pKa	13.63	ChemAxon Molconvert
hydrogen acceptor count	6	ChemAxon Molconvert
hydrogen donor count	2	ChemAxon Molconvert
polar surface area	99.60	ChemAxon Molconvert
rotatable bond count	2	ChemAxon Molconvert
refractivity	93.06	ChemAxon Molconvert
polarizability	31.08	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D01767
PubChem Compound	5312154
PubChem Substance	46507303
ChemSpider	4471584
Therapeutic Targets Database	DAP000736
PharmGKB	PA13189062
Drug Product Database	2231120

ATC Codes

M01AC02

AHFS Codes

28:08.04.92

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (57.1 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

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 Gene: PTGS2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Kothekar V, Sahi S, Srinivasan M, Mohan A, Mishra J: Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study. Indian J Biochem Biophys. 2001 Feb-Apr;38(1-2):56-63. Pubmed Yamada M, Niki H, Yamashita M, Mue S, Ohuchi K: Prostaglandin E2 production dependent upon cyclooxygenase-1 and cyclooxygenase-2 and its contradictory modulation by auranofin in rat peritoneal macrophages. J Pharmacol Exp Ther. 1997 May;281(2):1005-12. Pubmed Ozgocmen S, Ardicoglu O, Erdogan H, Fadillioglu E, Gudul H: In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of patients with knee osteoarthritis. Ann Clin Lab Sci. 2005 Spring;35(2):137-43. Pubmed Yilmaz H, Gurel S, Ozdemir O: The use and safety profile of non-steroidal antiinflammatory drugs among Turkish patients with osteoarthritis. Turk J Gastroenterol. 2005 Sep;16(3):138-42. Pubmed Galvao RI, Diogenes JP, Maia GC, Filho EA, Vasconcelos SM, de Menezes DB, Cunha GM, Viana GS: Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats. Neurochem Res. 2005 Jan;30(1):39-46. Pubmed 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 Pharmacological action: unknown 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 Gene: PTGS1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Yamada M, Niki H, Yamashita M, Mue S, Ohuchi K: Prostaglandin E2 production dependent upon cyclooxygenase-1 and cyclooxygenase-2 and its contradictory modulation by auranofin in rat peritoneal macrophages. J Pharmacol Exp Ther. 1997 May;281(2):1005-12. Pubmed Ozgocmen S, Ardicoglu O, Erdogan H, Fadillioglu E, Gudul H: In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of patients with knee osteoarthritis. Ann Clin Lab Sci. 2005 Spring;35(2):137-43. Pubmed Lucio M, Ferreira H, Lima JL, Reis S: Interactions between oxicams and membrane bilayers: an explanation for their different COX selectivity. Med Chem. 2006 Sep;2(5):447-56. Pubmed Lora M, Morisset S, Menard HA, Leduc R, de Brum-Fernandes AJ: Expression of recombinant human cyclooxygenase isoenzymes in transfected COS-7 cells in vitro and inhibition by tenoxicam, indomethacin and aspirin. Prostaglandins Leukot Essent Fatty Acids. 1997 May;56(5):361-7. Pubmed Kothekar V, Sahi S, Srinivasan M, Mohan A, Mishra J: Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study. Indian J Biochem Biophys. 2001 Feb-Apr;38(1-2):56-63. Pubmed

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:

Kothekar V, Sahi S, Srinivasan M, Mohan A, Mishra J: Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study. Indian J Biochem Biophys. 2001 Feb-Apr;38(1-2):56-63. Pubmed
Yamada M, Niki H, Yamashita M, Mue S, Ohuchi K: Prostaglandin E2 production dependent upon cyclooxygenase-1 and cyclooxygenase-2 and its contradictory modulation by auranofin in rat peritoneal macrophages. J Pharmacol Exp Ther. 1997 May;281(2):1005-12. Pubmed
Ozgocmen S, Ardicoglu O, Erdogan H, Fadillioglu E, Gudul H: In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of patients with knee osteoarthritis. Ann Clin Lab Sci. 2005 Spring;35(2):137-43. Pubmed
Yilmaz H, Gurel S, Ozdemir O: The use and safety profile of non-steroidal antiinflammatory drugs among Turkish patients with osteoarthritis. Turk J Gastroenterol. 2005 Sep;16(3):138-42. Pubmed
Galvao RI, Diogenes JP, Maia GC, Filho EA, Vasconcelos SM, de Menezes DB, Cunha GM, Viana GS: Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats. Neurochem Res. 2005 Jan;30(1):39-46. Pubmed
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

Pharmacological action: unknown
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:

Yamada M, Niki H, Yamashita M, Mue S, Ohuchi K: Prostaglandin E2 production dependent upon cyclooxygenase-1 and cyclooxygenase-2 and its contradictory modulation by auranofin in rat peritoneal macrophages. J Pharmacol Exp Ther. 1997 May;281(2):1005-12. Pubmed
Ozgocmen S, Ardicoglu O, Erdogan H, Fadillioglu E, Gudul H: In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of patients with knee osteoarthritis. Ann Clin Lab Sci. 2005 Spring;35(2):137-43. Pubmed
Lucio M, Ferreira H, Lima JL, Reis S: Interactions between oxicams and membrane bilayers: an explanation for their different COX selectivity. Med Chem. 2006 Sep;2(5):447-56. Pubmed
Lora M, Morisset S, Menard HA, Leduc R, de Brum-Fernandes AJ: Expression of recombinant human cyclooxygenase isoenzymes in transfected COS-7 cells in vitro and inhibition by tenoxicam, indomethacin and aspirin. Prostaglandins Leukot Essent Fatty Acids. 1997 May;56(5):361-7. Pubmed
Kothekar V, Sahi S, Srinivasan M, Mohan A, Mishra J: Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study. Indian J Biochem Biophys. 2001 Feb-Apr;38(1-2):56-63. Pubmed

Enzymes
1. Cytochrome P450 2C9 Actions: substrate 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 Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. Pubmed 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

Enzymes

1. Cytochrome P450 2C9

Actions: substrate

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:

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. Pubmed
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 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 Gene: SLC22A8 Protein Sequence: FASTA SNPs: SNPJam Report References: Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. Pubmed

Transporters

1. 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:

Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:39

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.