Ogino K, Hatanaka K, Kawamura M, Ohno T, Harada Y
Department of Pharmacology, Nippon Boehringer Ingelheim Co. Ltd., Kawanishi Pharma Research Institute, Kawanishi, Japan.
Pharmacology. 2000 Nov;61(4):244-50. doi: 10.1159/000028408.
We studied the effects of meloxicam on prostanoid levels, both in the inflammatory site in rat carrageenin-induced pleurisy and in the rat stomach injected with 1 mol/l NaCl solution, to clarify the relationship between its low gastric toxicity and its relative cyclooxygenase (COX) 2 selectivity. NS-398 (3 mg/kg), a highly selective COX-2 inhibitor, and meloxicam (3 mg/kg) exhibited anti-inflammatory effects in the pleurisy model. Prostaglandin (PG) E(2) thromboxane (TX) B(2) and 6-keto-PGF(1alpha) were detectable in the inflammatory site. Anti-inflammatory doses of NS-398 and meloxicam each suppressed the intrapleural PGE(2) level at 5 h as potently as piroxicam (3 mg/kg) as aspirin (100 mg/kg), both of which are nonselective COX inhibitors. NS-398 was much less potent than the other three in suppressing the levels of TXB(2) and 6-keto-PGF(1alpha). These results suggest that PGE(2) may be produced mainly via COX-2 in this model and that meloxicam may inhibit COX-2 in the inflammatory site. Piroxicam completely inhibited the increase in gastric PGE(2) induced by administering 1 mol/l NaCl solution into the rat stomach. Nimesulide (3 mg/kg), another selective COX-2 inhibitor, however, never affected this increase, suggesting that the gastric PGE(2) may be produced via COX-1. The anti-inflammatory dose of meloxicam caused statistically nonsignificant suppression of the PGE(2) level, by approximately 50%. These results suggest that the potent anti-inflammatory effect of meloxicam, accompanied with low gastric toxicity, may be related to its relative selectivity for COX-2 over COX-1.
我们研究了美洛昔康对前列腺素水平的影响，包括在大鼠角叉菜胶诱导的胸膜炎炎症部位以及注射1 mol/l氯化钠溶液的大鼠胃中，以阐明其低胃毒性与其相对环氧化酶（COX）-2选择性之间的关系。NS-398（3 mg/kg），一种高度选择性的COX-2抑制剂，和美洛昔康（3 mg/kg）在胸膜炎模型中表现出抗炎作用。在炎症部位可检测到前列腺素（PG）E2、血栓素（TX）B2和6-酮-PGF1α。NS-398和美洛昔康的抗炎剂量在5小时时均能有效抑制胸膜内PGE2水平，其效力与吡罗昔康（3 mg/kg）和阿司匹林（100 mg/kg）相当，后两者均为非选择性COX抑制剂。NS-398在抑制TXB2和6-酮-PGF1α水平方面的效力远低于其他三者。这些结果表明，在该模型中PGE2可能主要通过COX-2产生，且美洛昔康可能在炎症部位抑制COX-2。吡罗昔康完全抑制了向大鼠胃内注射1 mol/l氯化钠溶液所诱导的胃PGE2增加。然而，另一种选择性COX-2抑制剂尼美舒利（3 mg/kg）从未影响这种增加，这表明胃PGE2可能通过COX-1产生。美洛昔康的抗炎剂量对PGE2水平产生了约50%的抑制作用，在统计学上无显著差异。这些结果表明，美洛昔康强大的抗炎作用及其低胃毒性可能与其对COX-2相对于COX-1的相对选择性有关。
