COMPARATIVE-STUDY OF GOITROGENIC ACTIONS OF 3-SUBSTITUTED 1,2,4-TRIAZOLES IN RATS

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 substituent s on the 3-position of 1, 2, 4-triazole (TZ), and those of the parenta l compound, were compared in rats. After administration of either ATZ, MTZ, or NTZ, the thyroids of rats were enlarged with decreasing of co lloid content and a proliferation of the follicular epithelia. The ser um concentration of 3, 5, 3'-triiodothyronine and thyroxine decreased, while that of thyroid-stimulating hormone increased. ATZ, MTZ, and NT Z inhibited thyroid peroxidase activity both in vivo and in vitro. The se antithyroid actions were the most remarkable in case of MTZ and wer e the least in case of NTZ. TZ had no effect on the thyroid function i n vivo and in vitro. The results of Lineweaver-Burk analysis on the ef fect to lactoperoxidase activity indicated that ATZ, MTZ, and NTZ show ed 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 im portant for induction of goiter in rats. A comparison of the relations hip between substituent on the 3-position of TZ and antithyroid activi ty shows that a mercapto moiety has more potent antithyroid action tha n an amino and a nitro moiety. It is concluded that the differences in antithyroid activity of TZ derivatives depend on the potency of the s ubstituents.