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新型巯基化合物2-巯基-2-甲基丙酰-L-半胱氨酸(SA96)的药理学研究。I. 抗风湿作用的评价(作者译)

[Pharmacological studies of new sulfhydryl compounds 2-mercapto-2-methylpropanoyl-L-cysteine (SA96). I. Evaluation of anti-rheumatic action (author's transl)].

作者信息

Fujimura H, Hiramatsu Y, Tamura Y, Yanagihara M, Koda A, Nagai H, Uda K, Iso T, Yamauchi H

出版信息

Nihon Yakurigaku Zasshi. 1980 Mar;76(2):117-29.

PMID:6249702
Abstract

Oral administration of 2-mercapto-2-methylpropanoyl-L-cysteine (SA 96), a newly synthesized sulfhydryl compound, showed protective and curative effects on adjuvant-induced arthritis in rats similarly to those seen with D-penicillamine (D-PA). However, the effects of these compounds were not dose-dependent, and the maximum effects of SA96 were observed at 10 mg/kg/day. On the contrary, SA96 and D-PA had little effect on the various acute and subacute inflammatory responses induced in rat and mice. Formation of hemolytic plaque forming cells in the spleen of mice immunized with 5 X 10(8) sheep red blood cells was potentiated by the oral administration of both compounds. These stimulatory effects of SA96 and D-PA on the humoral immune responses were also not dose-dependent, and the maximum effects of SA96 were observed with 10 mg/kg/day, as in the case of adjuvant-induced arthritis in rats. In in vitro experiments, the inactivation of rheumatoid factor and the inhibition of collagenase and bone alkaline phosphatase activities were observed with both compounds, but these effects of SA96 were more potent than those of D-PA. As there is a similarity in the pharmacological profiles of SA96 and D-PA, SA96 may prove to be clinically effective for rheumatoid arthritis.

摘要

口服一种新合成的巯基化合物2-巯基-2-甲基丙酰-L-半胱氨酸(SA 96),对大鼠佐剂性关节炎显示出与D-青霉胺(D-PA)类似的保护和治疗作用。然而,这些化合物的作用并非剂量依赖性,SA96在10mg/kg/天时观察到最大效应。相反,SA96和D-PA对大鼠和小鼠诱导的各种急性和亚急性炎症反应几乎没有影响。口服这两种化合物均可增强用5×10⁸个绵羊红细胞免疫的小鼠脾脏中溶血空斑形成细胞的形成。SA96和D-PA对体液免疫反应的这些刺激作用也不是剂量依赖性的,与大鼠佐剂性关节炎的情况一样,SA96在10mg/kg/天时观察到最大效应。在体外实验中,两种化合物均观察到类风湿因子的失活以及胶原酶和骨碱性磷酸酶活性的抑制,但SA96的这些作用比D-PA更强。由于SA96和D-PA的药理学特征相似,SA96可能被证明对类风湿性关节炎具有临床疗效。

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