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targets (2) transporters (1)
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Identification
Name Tolmetin
Accession Number DB00500 (APRD01268)
Type small molecule
Groups approved
Description

A non-steroidal anti-inflammatory agent (anti-inflammatory agents, NON-steroidal) similar in mode of action to indomethacin. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Tolmetin Sodium
  • Tolmetina [DCIT]
  • Tolmetine [INN-French]
  • Tolmetino [INN-Spanish]
  • Tolmetinum [INN-Latin]
Brand names
  • Tolectin
  • Tolectin DS
Brand name mixtures Not Available
Categories
  • Cyclooxygenase Inhibitors
CAS number 26171-23-3
Weight Average: 257.2845
Monoisotopic: 257.105193351
Chemical Formula C15H15NO3
InChI Key InChIKey=UPSPUYADGBWSHF-UHFFFAOYSA-N
InChI
InChI=1S/C15H15NO3/c1-10-3-5-11(6-4-10)15(19)13-8-7-12(16(13)2)9-14(17)18/h3-8H,9H2,1-2H3,(H,17,18)
Plain Text
IUPAC Name
2-{1-methyl-5-[(4-methylphenyl)carbonyl]-1H-pyrrol-2-yl}acetic acid
SMILES
CN1C(CC(O)=O)=CC=C1C(=O)C1=CC=C(C)C=C1
Plain Text
Mass Spec show (9.1 KB)
Taxonomy
Kingdom Organic
Classes
  • Benzoyl Derivatives
Substructures
  • Hydroxy Compounds
  • Acetates
  • Carboxylic Acids and Derivatives
  • Pyrroles
  • Benzene and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Benzoyl Derivatives
  • Ketones
Pharmacology
Indication For the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis, including the treatment of acute flares long-term management. Also for treatment of juvenile rheumatoid arthritis.
Pharmacodynamics Tolmetin is a nonsteroidal anti-inflammatory agent. Studies in animals have shown tolmetin to possess anti-inflammatory, analgesic and antipyretic activity. In the rat, tolmetin prevents the development of experimentally induced polyarthritis and also decreases established inflammation. In patients with either rheumatoid arthritis or osteaoarthritis, tolmetin is as effective as aspirin and indomethacin in controlling disease activity, but the frequency of the milder gastrointestinal adverse effects and tinnitus was less than in aspirin-treated patients, and the incidence of central nervous system adverse effects was less than in indomethacin-treated patients. In patients with juvenile rheumatoid arthritis, tolmetin is as effective as aspirin in controlling disease activity, with a similar incidence of adverse reactions. tolmetin has produced additional therapeutic benefit when added to a regimen of gold salts and, to a lesser extent, with corticosteroids. Tolmetin should not be used in conjunction with salicylates since greater benefit from the combination is not likely, but the potential for adverse reactions is increased.
Mechanism of action The mode of action of tolmetin is not known. However, studies in laboratory animals and man have demonstrated that the anti-inflammatory action of tolmetin is not due to pituitary-adrenal stimulation. Tolmetin inhibits prostaglandin synthetase in vitro and lowers the plasma level of prostaglandin E in man. This reduction in prostaglandin synthesis may be responsible for the anti-inflammatory action. Tolmetin does not appear to alter the course of the underlying disease in man.
Absorption Rapidly and almost completely absorbed with peak plasma levels being reached within 30-60 minutes after an oral therapeutic dose.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Essentially all of the administered dose is recovered in the urine in 24 hours either as an inactive oxidative metabolite or as conjugates of tolmetin.
Route of elimination Not Available
Half life Biphasic elimination from the plasma consisting of a rapid phase with a half-life of one to 2 hours followed by a slower phase with a half-life of about 5 hours.
Clearance Not Available
Toxicity Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ortho mcneil janssen pharmaceuticals inc
  • Actavis elizabeth llc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Tablet Oral
Prices
Unit description Cost Unit
Tolectin 600 mg tablet 2.43 USD tablet
Tolmetin sodium 600 mg tablet 2.06 USD tablet
Tolmetin Sodium 400 mg capsule 1.77 USD capsule
Tolmetin sodium 200 mg tablet 0.77 USD tablet
Patents Not Available
Properties
State solid
Melting point 156 oC
Experimental Properties
Property Value Source
water solubility 222 mg/L PhysProp
logP 2.6 PhysProp
pKa 3.5 Various sources
Predicted Properties
Property Value Source
water solubility 1.31e-01 g/l ALOGPS
logP 2.81 ALOGPS
logP 2.73 ChemAxon Molconvert
logS -3.29 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 59.30 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 72.39 ChemAxon Molconvert
polarizability 27.67 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C02328 Link_out
PubChem Compound 5509 Link_out
PubChem Substance 46507060 Link_out
ChemSpider 5308 Link_out
Therapeutic Targets Database DAP000777 Link_out
PharmGKB PA451721 Link_out
Drug Product Database 632740 Link_out
RxList http://www.rxlist.com/cgi/generic2/tolmetin.htm Link_out
Drugs.com http://www.drugs.com/cdi/tolmetin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tol1449.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Tolmetin Link_out
ATC Codes
  • M01AB03
  • M02AA21
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (77.4 KB)
MSDS show (44.3 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 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Burdan F, Szumilo J, Klepacz R, Dudka J, Korobowicz A, Tokarska E, Cendrowska-Pinkosz M, Madej B, Klepacz L: Gastrointestinal and hepatic toxicity of selective and non-selective cyclooxygenase-2 inhibitors in pregnant and non-pregnant rats. Pharmacol Res. 2004 Nov;50(5):533-43. Pubmed
  2. Capasso A, Sorrentino L: Arachidonic acid and its metabolites are involved in the expression of morphine dependence in guinea-pig isolated ileum. Eur J Pharmacol. 1997 Jul 9;330(2-3):199-204. Pubmed
  3. Kirkova M, Alexandova A, Kesiova M, Todorov S: In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems. Comparison with non-selective and COX-2 selective NSAIDs. Auton Autacoid Pharmacol. 2007 Apr;27(2):99-104. Pubmed
  4. Kennedy JH, Korn N, Thurston RJ: Prostaglandin levels in seminal plasma and sperm extracts of the domestic turkey, and the effects of cyclooxygenase inhibitors on sperm mobility. Reprod Biol Endocrinol. 2003 Oct 9;1:74. Pubmed
  5. Capasso A: Further studies on the involvement of the arachidonic acid cascade in the acute dependence produced by mu, kappa and delta opioid agonists in isolated tissues. Neuropharmacology. 1999 Jun;38(6):871-7. 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

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:
  1. Capasso A, Sorrentino L: Arachidonic acid and its metabolites are involved in the expression of morphine dependence in guinea-pig isolated ileum. Eur J Pharmacol. 1997 Jul 9;330(2-3):199-204. Pubmed
  2. Kennedy JH, Korn N, Thurston RJ: Prostaglandin levels in seminal plasma and sperm extracts of the domestic turkey, and the effects of cyclooxygenase inhibitors on sperm mobility. Reprod Biol Endocrinol. 2003 Oct 9;1:74. Pubmed
  3. Capasso A: Further studies on the involvement of the arachidonic acid cascade in the acute dependence produced by mu, kappa and delta opioid agonists in isolated tissues. Neuropharmacology. 1999 Jun;38(6):871-7. Pubmed
  4. Burdan F, Szumilo J, Marzec B, Klepacz R, Dudka J: Skeletal developmental effects of selective and nonselective cyclooxygenase-2 inhibitors administered through organogenesis and fetogenesis in Wistar CRL:(WI)WUBR rats. Toxicology. 2005 Dec 15;216(2-3):204-23. Epub 2005 Sep 22. 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. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:40

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