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

Site of Analgesic Action of a Non‐steroidal, Antiinflammatory Drug, Tolmetin Sodium, in Rats

“…Time-course of anti-writhing activity of tolmetin sodium Anti-writhing ED50 values of tolmetin sodium and aspirin have been reported to be 3.01 and 25.0 mg/kg orally, respectively, in the rat acetic acid-writhing test (Nakamura et al, 1979b). Tolmetin sodium 3 mg/kg or aspirin 25 mg/kg was given orally to the rat 15, 30, 45 and 55 min after acetic acid injection and 45, 30, 15 and 5 min later, respectively, anti-writhing activity was measured.…”

“…It is considered that tolmetin sodium produces its analgesic action mainly by a peripheral mechanism since this drug, like aspirin, has anti-inflammatory and anti-pyretic activities (Wong et al, 1973;Shimizu et al, 1975a;Nakamura et al, 1979b) but has no effect on the central nervous system (Shimizu, Matsuno, Soji, Kawashima, Ito & Hori, 1975b). If tolmetin sodium acts peripherally, a sufficient quantity of tolmetin to produce anti-writhing action should be found in the peritoneal cavity after oral administration and also, the anti-writhing action of tolmetin sodium should be produced by intraperitoneal (local) administration of lower doses than those used for intravenous (systemic) administration.…”

“…Only rats showing the wri-thing syndrome within 15 min after acetic acid injection, were used for the experiment. Drugs were administered to the rats between 15 to 60 min after the acetic acid injection and then the number of writhings was counted for 20 min, beginning at 60 min after the acetic acid injection (Niemegeers, Van Bruggen & Janssen, 1975;Nakamura et al, 1979b).…”

“…In experimental animals, it has been reported that tolmetin sodium has relatively more potent analgesic (anti-writhing) activity than anti-inflammatory activity, while it shows inhibitory activities on many kinds of experimentally induced inflammations (Wong, Gardocki & Pruss, 1973;Shimizu, Nakamura, Motoyoshi & Yokoyama, 1975;Nakamura, Yokoyama, Motoyoshi, Ishii & Shimizu, 1979a;Nakamura, Ishii, Motoyoshi, Imazu, Yokoyama & Shimizu, 1979b). Anti-writhing activity of tolmetin sodium has been reported to be 10 times or more that of aspirin and 2 to 10 times that of ibuprofen in the mouse writhing tests, using phenylquinone, acetylcholine and acetic acid as algesic chemicals (Wong et al, 1973;Shimizu et al, 1975;Nakamura et al, 1979b), and to be about 8 and about 4 times as potent as aspirin and ibuprofen, respectively, in the rat acetic acid-writhing test (Nakamura et al, 1979b). Tolmetin sodium, however, does not show analgesic 0007-1188/81/070779-07 $01.00 activity in the tail flick or Haffner tests, and its anti-writhing action is not reversed by naloxone, nor is it influenced by repeated administration (Nakamura, Ishii, Yokoyama, Motoyoshi, Imazu & Shimizu, 1977).…”

Colon-Specific Drug Delivery Based on a Cyclodextrin Prodrug: Release Behavior of Biphenylylacetic Acid from Its Cyclodextrin Conjugates in Rat Intestinal Tracts after Oral Administration

“…Evaluation of Antiinflammatory ResponsessThis method was based on that of Nakamura et al 24 The paw swelling of male Wistar rats (about 180 g) was volumetrically determined using a water plethysmometer. 25 A 1%(w/v) carrageenan (Code 073-50, Lot M6P3336, Nacalai Tesque, Tokyo, Japan) in saline (0.1 mL) solution was injected subcutaneously into the right hind paw at various times after the samples had been administered orally (equivalent to 10 mg of BPAA/5 mL of water per kg of rat body weight).…”