Abstract
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 micrograms/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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