Nakamura H, Ishii K, Motoyoshi S, Imazu C, Yokoyama Y, Shimizu M
Nihon Yakurigaku Zasshi. 1979 May;75(4):405-17. doi: 10.1254/fpj.75.405.
Effect of tolmetin sodium on the pain-like responses caused by various nociceptive stimuli was examined in experimental animals. 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, p.o.) was about 2.4--10.3 times that of ibuprofen and aspirin. The hypertension induced by intraarterial 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 PGE1 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-carrageenin or adjuvant was inhibited by tolmetin sodium (30--100 or 20--40 mg/kg, p.o., respectively), and the potency was approximately equal that of 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. From these results, it was concluded that 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.
在实验动物中研究了托美丁钠对各种伤害性刺激引起的疼痛样反应的影响。托美丁钠对小鼠和大鼠醋酸诱导的扭体反应显示出强效抑制活性,其效力(口服半数有效剂量ED50分别为23.4和3.01mg/kg)约为布洛芬和阿司匹林的2.4 - 10.3倍。向犬脾脏动脉内注射缓激肽诱导的高血压被托美丁钠抑制(静脉注射半数有效剂量ED50 = 80mg/kg),但同时注射缓激肽和前列腺素E1引起的高血压未被托美丁钠和安乃近抑制,尽管喷他佐辛可抑制这两种高血压。高岭土 - 角叉菜胶或佐剂诱导的大鼠炎症爪子或关节受到机械压迫所引起的疼痛样反应被托美丁钠抑制(口服分别为30 - 100或20 - 40mg/kg),其效力与布洛芬和保泰松大致相当。托美丁钠对犬牙髓电刺激诱导的疼痛样反应产生显著抑制,但应用哈夫纳和达莫尔 - 史密斯方法时对小鼠无作用。托美丁钠的抗扭体作用未被纳洛酮拮抗。从这些结果得出结论,托美丁钠对化学伤害性刺激和炎症组织的机械压力刺激诱导的疼痛样反应具有强效抑制活性,尤其是对扭体反应。其镇痛活性可能涉及外周机制。