Takaoka M, Manabe S, Yamoto T, Teranishi M, Matsunuma N, Masuda H, Goto N
Laboratory Animal Science, Sankyo Co., Ltd. Shizuoka, Japan.
J Vet Med Sci. 1994 Apr;56(2):341-6. doi: 10.1292/jvms.56.341.
Antithyroid actions of 3-amino-1, 2, 4-triazole (ATZ), 3-mercapto-1, 2, 4-triazole (MTZ) and 3-nitro-1, 2, 4-triazole (NTZ), which are substituents on the 3-position of 1, 2, 4-triazole (TZ), and those of the parental compound, were compared in rats. After administration of either ATZ, MTZ, or NTZ, the thyroids of rats were enlarged with decreasing of colloid content and a proliferation of the follicular epithelia. The serum concentration of 3, 5, 3'-triiodothyronine and thyroxine decreased, while that of thyroid-stimulating hormone increased. ATZ, MTZ, and NTZ inhibited thyroid peroxidase activity both in vivo and in vitro. These antithyroid actions were the most remarkable in case of MTZ and were the least in case of NTZ. TZ had no effect on the thyroid function in vivo and in vitro. The results of Lineweaver-Burk analysis on the effect to lactoperoxidase activity indicated that ATZ, MTZ, and NTZ showed competitive inhibition. These results suggest that both MTZ and NTZ have goitrogenic effects on the thyroid through antiperoxidase action, such as ATZ. Thus, the 3rd carbon position of TZ is thought to be important for induction of goiter in rats. A comparison of the relationship between substituent on the 3-position of TZ and antithyroid activity shows that a mercapto moiety has more potent antithyroid action than an amino and a nitro moiety. It is concluded that the differences in antithyroid activity of TZ derivatives depend on the potency of the substituents.
比较了1,2,4 - 三唑（TZ）3位上的取代物3 - 氨基 - 1,2,4 - 三唑（ATZ）、3 - 巯基 - 1,2,4 - 三唑（MTZ）和3 - 硝基 - 1,2,4 - 三唑（NTZ）及其母体化合物对大鼠的抗甲状腺作用。给予ATZ、MTZ或NTZ后，大鼠甲状腺肿大，胶体含量减少，滤泡上皮细胞增殖。血清中3,5,3'-三碘甲状腺原氨酸和甲状腺素浓度降低，而促甲状腺激素浓度升高。ATZ、MTZ和NTZ在体内和体外均抑制甲状腺过氧化物酶活性。这些抗甲状腺作用在MTZ情况下最为显著，在NTZ情况下最不明显。TZ在体内和体外对甲状腺功能均无影响。对乳过氧化物酶活性影响的Lineweaver - Burk分析结果表明，ATZ、MTZ和NTZ表现出竞争性抑制。这些结果表明，MTZ和NTZ都通过抗过氧化物酶作用对甲状腺产生致甲状腺肿作用，如ATZ。因此，TZ的第3个碳原子位置被认为对大鼠甲状腺肿的诱导很重要。比较TZ 3位上的取代基与抗甲状腺活性之间的关系表明，巯基部分比氨基和硝基部分具有更强的抗甲状腺作用。得出的结论是，TZ衍生物抗甲状腺活性的差异取决于取代基的效力。
