Analgesic activity of a non-steroidal anti-inflammatory agent, tolmetin sodium in experimental animals

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Abstract
Effect of tolmetin sodium on the pain-like responses caused by various nociceptive stimuli was studied in mice, dogs and rats. Tolmetin sodium showed a potent inhibitory activity on the acetic acid-induced writhing in mice and rats, and its potency (ED50'' = 23.4 and 3.01 mg/kg orally) was about 2.4-10.3 times that of ibuprofen and aspirin. The hypertension induced by intra-arterial injection of bradykinin toward the spleen of dogs was inhibited by tolmetin sodium (ED50 = 80 mg/kg i.v.), but the hypertension by a simultaneous injection of bradykinin and PG[prostaglandin]E1 was not inhibited by tolmetin sodium and sulpyrine, though pentazocine inhibited both hypertensions. The pain-like response caused by pressing mechanically the inflamed paws or joints of rats induced by kaolin-carrageenan or adjuvant was inhibited by tolmetin sodium (30-100 or 20-40 mg/kg orally, respectively), and the potency was approximately equal to ibuprofen and phenylbutazone. Tolmetin sodium produced a significant inhibition of the pain-like response induced by electrical stimulation of tooth pulp of dogs, but showed no effect when the methods of Haffner and D''Amour-Smith were applied to mice. Anti-writhing action of tolmetin sodium was not antagonized by naloxone. Apparently, tolmetin sodium has a potent inhibitory activity on the pain-like responses induced by the chemical nociceptive stimuli and by the mechanical pressure stimulus of the inflamed tissue, especially on the writhing. The analgesic activity probably involves a peripheral mechanism.