THE MECHANISM OF INCREASED THYROIDAL FUNCTION CAUSED BY (±)-4-DIETHYLAMINO-1, 1-DIMETHYLBUT-2-YN-1-YL 2-CYCLOHEXYL-2-HYDROXY2-PHENYLACETATE MONOHYDROCHLORIDE MONOHYDRIDTE(NS-21), A NOVEL DRUG FOR URINARY FREQUENCY AND INCONTINENCE, ADMINISTRATION IN RATS

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  • 新規頻尿・尿失禁治療剤 (±)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydtoxy-2-phenylacetate monohydrochloride monohydrate (NS-21) のラットにおける甲状腺機能充進の機序
  • 新規頻尿・尿失禁治療剤(+)-4-diethylamino-1,1-dimethylbut-2yn-1-yl2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21)のラットにおける甲状腺機能亢進の機序
  • シンキ ヒンニョウ ニョウ シッキン チリョウザイ+4 diethylamin

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A study was conducted to elucidate the mechanism of the increased thyroidal function caused by oral administration of (±)-4-diethylamino-1, 1-dimethylbut-2-yn- 1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, in rats. Rats were given 500 mg/kg of NS-21 orally for 13 weeks. Rats were also given 500 mg/kg of the drug and 15 μg/animal of thyroxine (T4) in order to assess the influence of T4 treatment. NS-21 caused decreases in both total and free T4 and increases in TSH and thyroxine uridine diphosphate glucuronyltransferase (T4UDP-GT). Morphological examination of thyroid gland revealed stimulated follicles indicating heightened thyroidal function. The treatment of T4 inhibited the stimulating effect of NS-21 on thyroid gland. These results show that the administration of NS-21 caused induction of T4UDP-GT, which resulted in a compensatory stimulation of the thyroidal function by the increased secretion of pituitary TSH in response to increased blood thyroid hormone metabolism.

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