| Identification | Back Directory | [Name]
Tolmetin sodium | [CAS]
35711-34-3 | [Synonyms]
TOLECTIN
TOLMETIN SODIUM
Sodium tolmetin
Tolmetin Sodium Salt
Tolmetin sodium USP/EP/BP
sodium 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate
1-Methyl-5-p-toluoyl-1H-pyrrole-2-acetic acid sodium salt
sodium:2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetate
1-Methyl-5-(p-toluoyl)-1H-pyrrole-2-acetic acid sodium salt
SodiuM 2-(1-Methyl-5-(4-Methylbenzoyl)-1H-pyrrol-2-yl)acetate
tolmetin sodium:sodium 1-methyl-5-(4-methylbenzoyl)-1h-pyrrole-2-acetate | [EINECS(EC#)]
252-687-3 | [Molecular Formula]
C15H14NNaO3 | [MDL Number]
MFCD00079607 | [MOL File]
35711-34-3.mol | [Molecular Weight]
279.27 |
| Hazard Information | Back Directory | [Originator]
Tolectin,McNeil,US,1976 | [Uses]
Tolectin (Ortho-McNeil). | [Uses]
Tolmetin Sodium is a non-steroidal anti-inflammatory drug. | [Definition]
ChEBI: Tolmetin sodium is an organic sodium salt that is the monosodium salt of tolmetin. Used in the form of its dihydrate as a nonselective nonsteroidal anti-inflammatory drug. It has a role as an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor and a non-steroidal anti-inflammatory drug. It contains a tolmetin(1-). | [Manufacturing Process]
5-(p-Toluoyl)-1-methylpyrrole-2-acetonitrile - To a cooled suspension of 26.6 g
(0.2 mol) aluminum chloride in 80 ml dichloroethane is added dropwise 30.8 g
(0.2 mol) p-toluoyl chloride. The resulting solution is added dropwise to a
solution of 1-methylpyrrole-2-acetonitrile in 80 ml dichloroethane cooled
externally with an ice bath. After the addition, the resulting solution is stirred
at room temperature for 20 minutes and then refluxed for 3 minutes. The
solution is poured into ice acidified with dilute hydrochloric acid. The organic
and aqueous fractions are separated. The aqueous fraction is extracted once
with chloroform.
The organic fractions are combined and washed successively with N,N_x0002_dimethyl-1,3-propanediamine, dilute hydrochloric acid, saturated sodium
bicarbonate solution and saturated sodium chloride solution. The organic
fraction is dried over anhydrous magnesium sulfate. The solvent is then
evaporated off. Upon trituration of the residue with methanol, a solid
crystallizes, 5-(p-toluoyl)-1-methylpyrrole-2-acetonitrile, which is removed by
filtration and purified by recrystallization from benzene.
Additional product is isolated from the mother liquors which are combined,
concentrated in vacuo and the resulting oily residue column chromatographed
on neutral alumina using hexane, benzene and ether as successive solvents.
The product is isolated by concentrating in vacuo the first few major
compound-bearing fractions (10% ether in benzene). The solids are combined
and recrystallized from methanol and then from benzene-hexane, melting
point 102°C to 105°C.
5-(p-Toluoyl)-1-methylpyrrole-2-acetic acid - A solution of 3.67 g (0.015 mol)
of 5-(p-toluoyl)-1-methylpyrrole-2-acetonitrile, 24 ml of 1 N sodium hydroxide
and 50 ml of 95% ethanol is stirred and refluxed for 24 hours.
The resulting solution is poured into ice acidified with dilute hydrochloric acid.
A white solid precipitates which is extracted into ether. The ether phase is
washed with a saturated solution of sodium chloride and dried over anhydrous
magnesium sulfate. The solvent is evaporated and a white solid, 5-(p-toluoyl)-
1-methylpyrrole-2-acetic acid is obtained which is recrystallized twice from
isopropanol, melting point 155°C to 157°C. | [Therapeutic Function]
Antiinflammatory | [Pharmacokinetics]
Tolmetin sodium is rapidly and almost completely absorbed on oral administration, with peak plasma levels being
attained within the first hour of administration. It has a relatively short plasma half-life of approximately 1 hour
because of extensive first-pass metabolism, involving hydroxylation of the p-methyl group to the primary alcohol,
which is subsequently oxidized to the dicarboxylic acid. | [Clinical Use]
Tolmetin is synthesized straightforwardly from 1-methylpyrrole. It was introduced in the United States in 1976 and like other NSAIDs, inhibits prostaglandin biosynthesis. Tolmetin, however, also inhibits polymorph migration and
decreases capillary permeability. Its anti-inflammatory activity, as measured in the carrageenan-induced rat paw
edema and cotton pellet granuloma assays, is intermediate between those of phenylbutazone and indomethacin. | [Side effects]
The most frequently adverse reactions are those involving the GI tract (e.g., abdominal pain, discomfort, and nausea)
but appear to be less than those observed with aspirin. The CNS effects (e.g., dizziness and drowsiness) also are
observed. Few cases of overdosage have been reported, but in such cases, recommended treatment includes
elimination of the drug from the GI tract by emesis or gastric lavage and elimination of the acidic drug from the
circulatory system by enhancing alkalinization of the urine with sodium bicarbonate. | [Metabolism]
This metabolite is inactive in standard in vivo
anti-inflammatory assays. The free acid (pKa = 3.5) is highly bound to plasma proteins (99%), and excretion of
tolmetin and its metabolites occurs primarily in the urine.Approximately 15 to 20% of an administered dose is excreted unchanged and 10% as the glucuronide conjugate of
the parent drug. Conjugates of the dicarboxylic acid metabolite account for the majority of the remaining administered
drug. |
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