Mizoule J, Le Fur G, Uzan A
Arch Int Pharmacodyn Ther. 1979 Apr;238(2):305-32.
Two derivatives from a new heteroarylacetic series, 1,3,4-triphenylpyrazole-5-acetic acid (LM 22102) and 1-isobutyl-3,4-diphenylpyrazole-5-acetic acid (LM 22070), were selected on the basis of their anti-inflammatory, analgesic and antipyretic properties. In the mouse, LM 22102 and LM 22070 were respectively 15 and 30 times less active than indomethacin in Koster's test, but they were 9 and 13 times less toxic than the reference drugs. In contrast, they were very active in the rat and the guinea-pig. LM 22102 appeared to be as active as indomethacin in the various tests performed: Randall and Selitto's test for analgesic activity, hyperthermic rat, experimental models of inflammation (UV erythema, carrageenin-induced oedema, cotton granuloma, adjuvant-induced arthritis). In vitro, its inhibition of prostaglandin-synthetase in guinea-pig lung was appreciably more powerful than that of indomethacin. Like all potent non-steroid anti-inflammatory drugs it has ulcerogenic activity, similar to that of indomethacin, which accounts for its acute oral toxicity in the rat. The activity of LM 22070 is either the same as (antipyretic action) or inferior to (analgesic and anti-inflammatory activity and inhibition of prostaglandin-synthetase) that of indomethacin, but always markedly superior to that of phenylbutazone. Its ulcerogenic activity and oral acute toxicity in the rat are respectively 2.5 and 3 times weaker than those of indomethacin.
从新的杂芳基乙酸系列中选取了两种衍生物，即1,3,4-三苯基吡唑-5-乙酸（LM 22102）和1-异丁基-3,4-二苯基吡唑-5-乙酸（LM 22070），它们具有抗炎、镇痛和解热特性。在小鼠中，LM 22102和LM 22070在科斯特试验中的活性分别比吲哚美辛低15倍和30倍，但它们的毒性比参比药物低9倍和13倍。相比之下，它们在大鼠和豚鼠中活性很高。在进行的各种试验中，LM 22102似乎与吲哚美辛活性相当：兰德尔和塞利托的镇痛活性试验、发热大鼠试验、炎症实验模型（紫外线红斑、角叉菜胶诱导的水肿、棉球肉芽肿、佐剂诱导的关节炎）。在体外，它对豚鼠肺中前列腺素合成酶的抑制作用明显比吲哚美辛更强。与所有强效非甾体抗炎药一样，它具有致溃疡活性，与吲哚美辛相似，这也是其在大鼠中的急性口服毒性的原因。LM 22070的活性与吲哚美辛相同（解热作用）或低于吲哚美辛（镇痛和抗炎活性以及对前列腺素合成酶的抑制作用），但始终明显优于保泰松。它在大鼠中的致溃疡活性和口服急性毒性分别比吲哚美辛弱2.5倍和3倍。
