Antinociceptive activity of a novel non-steroidal anti-inflammatory drug (M-5011) with low ulcerogenic effects in mice.
Antinociceptive activity of a novel non-steroidal anti-inflammatory drug (M-5011) with low ulcerogenic effects in mice.
复制标题
一种新型非甾体抗炎药 (M-5011) 的镇痛活性，对小鼠具有较低的溃疡形成作用。
DOI：
10.1254/jjp.72.29
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
T. Naruse
中科院分区：
文献类型：
--
作者：
N. Murakami;H. Takase;T. Tomita;K. Iwata;T. Naruse
本文比较了新型非甾体抗炎药（NSAID） d-2-[4-（3-甲基-2-噻吩基）苯基]丙酸（M-5011）与吲哚美辛（IND）、酮洛芬（KP）、双氯芬酸钠（DIF）、扎尔托洛芬（ZLT）和tiaprofenic acid （TIA）在小鼠体内的镇痛和致溃疡活性。包括M-5011在内的所有口服非甾体抗炎药均以剂量依赖的方式抑制高岭土诱导的扭动。M-5011的有效抗伤活性（ED50值）为0.63 mg/kg，高于ZLT （16.80 mg/kg）和TIA (4.78 mg/kg)，与DIF （0.68 mg/kg）相当，低于IND （0.21 mg/kg）和KP （0.28 mg/kg）。在高岭土诱导的剧烈扭转时间（注射高岭土后7.5分钟），所有药物均显著降低腹膜6-酮前列腺素F1 α（6-酮- pgf1 α）水平，而不影响腹膜缓激素（BK）水平。所有药物的抗伤害性作用均与抑制腹膜6-酮- pgf1 α水平密切相关。M-5011在胃和小肠的致溃疡活性（UD50值）分别为88.23和46.09 mg/kg。其他药物在胃和小肠中的UD50值分别为：IND、KP、DIF、TIA和ZLT分别为8.96和4.78 mg/kg、20.04和10.75 mg/kg、4.19和2.24 mg/kg、62.86和46.55 mg/kg、110.92和54.78 mg/kg。由此可见，M-5011、IND、KP、DIF、TIA和ZLT的胃（或小肠）安全指数（UD50/ED50）分别为140.05（73.16）、42.67（22.76）、71.57（38.39）、6.16（3.29）、13.15（9.74）和6.60（3.26）。这些发现表明M-5011是一种有用的非甾体抗炎药，具有较低的致溃疡活性。
Both analgesic and ulcerogenic activities of d-2-[4-(3-methyl-2-thienyl)phenyl] propionic acid (M-5011), a novel non-steroidal anti-inflammatory drug (NSAID), were compared with those of indomethacin (IND), ketoprofen (KP), diclofenac sodium (DIF), zaltoprofen (ZLT) and tiaprofenic acid (TIA) in mice. All orally administered NSAIDs including M-5011 inhibited kaolin-induced writhing in a dose-dependent manner. M-5011 had an effective antinociceptive activity (ED50 value) of 0.63 mg/kg, being more potent than ZLT (16.80 mg/kg) and TIA (4.78 mg/kg), equipotent to DIF (0.68 mg/kg), and less potent than IND (0.21 mg/kg) and KP (0.28 mg/kg). All drugs tested significantly reduced peritoneal 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) levels at the peak kaolin-induced writhing time (7.5 min post-kaolin injection) without affecting peritoneal bradykinin (BK) levels. Antinociceptive effects of all drugs were closely correlated with inhibition of peritoneal 6-keto-PGF1 alpha levels. Ulcerogenic activities (UD50 value) of M-5011 in the stomach and small intestines were 88.23 and 46.09 mg/kg, respectively. UD50 values of other drugs in the stomach and small intestines were as follows: 8.96 and 4.78 mg/kg, 20.04 and 10.75 mg/kg, 4.19 and 2.24 mg/kg, 62.86 and 46.55 mg/kg, and 110.92 and 54.78 mg/kg for IND, KP, DIF, TIA, and ZLT, respectively. Thus, the safety indexes (UD50/ED50) of the stomach (or small intestine) for M-5011, IND, KP, DIF, TIA and ZLT were 140.05 (73.16), 42.67 (22.76), 71.57 (38.39), 6.16 (3.29), 13.15 (9.74) and 6.60 (3.26), respectively. These findings suggest that M-5011 is a useful NSAID that shows potent antinociceptive effects with low ulcerogenic activities.
DOI：
10.1073/pnas.85.5.1412
发表时间：
1988-03-01
影响因子：
11.1
作者：
DEWITT, DL;SMITH, WL
通讯作者：
SMITH, WL