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 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.
Takaoka
M
M
Laboratory Animal Science, Sankyo Co., Ltd. Shizuoka, Japan.
Manabe
S
S
Yamoto
T
T
Teranishi
M
M
Matsunuma
N
N
Masuda
H
H
Goto
N
N
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006042:Goiter / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014230:Triazoles / Q000633:toxicity*; D014284:Triiodothyronine / Q000097:blood
D014230:Triazoles; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine