Site of analgesic action of a non-steroidal, anti-inflammatory drug, tolmetin sodium, in rats

Abstract

1 The site of the analgesic action of tolmetin sodium was investigated by use of the acetic acid writhing test in rats. 2 Tolmetin sodium was administered to the rat between 15 and 60 min after intraperitoneal injection of 1 ml of a 1% acetic acid aqueous solution. Number of writhing was counted for 20 min beginning from 60 min after acetic acid injection. 3 When the rat was given tolmetin sodium 5 mg/kg orally, a relatively large quantity of tolmetin was found in the peritoneal exudate and there was a rough correlation between anti-writhing activity and the exudate tolmetin content. 4 Anti-writhing ED50 of tolmetin sodium was 1.42 (0.82-2.91) and 92.0 (57.0-140) microgram/kg when given intraperitoneally and intravenously, respectively, and the potency ratio of intraperitoneal to intravenous tolmetin sodium was 40.0 (18.5-80.2). This potency ratio for salicylic acid and morphine hydrochloride was 19.4 and 1.0, respectively. 5 When equipotent doses ( 5 microgram/kg i.p.; 200 microgram/kg i.v.) of tolmetin sodium were administered to the rat, the plasma tolmetin level after the intraperitoneal administration was less than one-fortieth that after the intravenous administration during the counting time of 20 min, while both the peritoneal exudate contents of tolmetin were nearly equal. 6 From these results, it is concluded that the site of anti-writhing action of tolmetin sodium is in the peritoneum and that tolmetin sodium produces its anti-writhing action mainly by a peripheral mechanism in the rat.