Engelhardt G, Bögel R, Schnitzler C, Utzmann R
Department of Pharmacological Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.
Biochem Pharmacol. 1996 Jan 12;51(1):29-38. doi: 10.1016/0006-2952(95)02110-8.
Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Preclinical studies have indicated that meloxicam has potent anti-inflammatory activity, together with a good gastrointestinal and renal tolerability profile. This report summarizes studies undertaken to compare meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase (COX-2) in inflamed areas (pleurisy of the rat, peritonitis of mice) and their influence on the activity of the constitutive cyclooxygenase (COX-1) in stomach, kidney, brain, and blood. In pleurisy of the rat, meloxicam was twice as potent as tenoxicam, 3 times as potent as flurbiprofen, 8 times as potent as diclofenac, and 20 times as potent as tenidap at inhibiting prostaglandin E2 (PGE2) biosynthesis. In the peritonitis model in mice, meloxicam was approximately twice as active as piroxicam, and more than 10 times as active as diclofenac in the suppression of PGE biosynthesis. Doses of meloxicam sufficient to inhibit PGE2 biosynthesis in the pleural exudate and peritoneal exudate had no influence on leukotriene-B4 (LTB4) or leukotriene-C4 (LTC4) content. The effect of meloxicam on the PGE2 content of rat gastric juice and rat urine was weaker than that of piroxicam or diclofenac. Meloxicam was a weaker inhibitor of the increased PGE2 concentration in brain of rats and mice (induced by convulsant doses of pentetrazole) than piroxicam, diclofenac, or indomethacin. Meloxicam had a weaker effect on serum thromboxane-B2 (TXB2) concentration in rats than piroxicam or tenoxicam. The in vivo findings confirm the results of in vitro tests, conducted separately, showing that meloxicam preferentially inhibits COX-2 over COX-1. COX-2 is the inducible isoenzyme implicated in the inflammatory response, whereas COX-1 has cytoprotective effects in the gastric mucosa. Therefore, a preferential selectivity for one isoenzyme over another, as displayed by meloxicam, may have implications in the clinical setting in terms of a more favorable risk: benefit profile.
美洛昔康是一种源自烯醇酸的新型非甾体抗炎药（NSAID）。临床前研究表明，美洛昔康具有强大的抗炎活性，同时具有良好的胃肠道和肾脏耐受性。本报告总结了为比较美洛昔康与其他NSAIDs在炎症部位（大鼠胸膜炎、小鼠腹膜炎）对诱导型环氧化酶（COX-2）的抑制作用及其对胃、肾、脑和血液中组成型环氧化酶（COX-1）活性的影响而进行的研究。在大鼠胸膜炎中，美洛昔康抑制前列腺素E2（PGE2）生物合成的效力是替诺昔康的两倍、氟比洛芬的3倍、双氯芬酸的8倍、替尼达普的20倍。在小鼠腹膜炎模型中，美洛昔康抑制PGE生物合成的活性约为吡罗昔康的两倍，比双氯芬酸高10倍以上。足以抑制胸腔积液和腹腔积液中PGE2生物合成的美洛昔康剂量对白三烯B4（LTB4）或白三烯C4（LTC4）含量没有影响。美洛昔康对大鼠胃液和大鼠尿液中PGE2含量的影响弱于吡罗昔康或双氯芬酸。美洛昔康对大鼠和小鼠脑中（由惊厥剂量的戊四氮诱导）PGE2浓度升高的抑制作用比吡罗昔康、双氯芬酸或吲哚美辛弱。美洛昔康对大鼠血清血栓素B2（TXB2）浓度的影响比吡罗昔康或替诺昔康弱。体内研究结果证实了单独进行的体外试验结果，表明美洛昔康对COX-2的抑制作用优于COX-1。COX-2是参与炎症反应的诱导型同工酶，而COX-1在胃黏膜中具有细胞保护作用。因此，美洛昔康对一种同工酶相对于另一种同工酶的优先选择性，在临床环境中可能意味着更有利的风险：效益比。
