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  • Title: Study of two new non-steroid anti-inflammatory drugs having a pyrazole structure (LM 22070 and LM 22102).
    Author: Mizoule J, Le Fur G, Uzan A.
    Journal: Arch Int Pharmacodyn Ther; 1979 Apr; 238(2):305-32. PubMed ID: 112931.
    Abstract:
    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.
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