[The mechanism of increased thyroidal function caused by (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, administration in rats].
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.
Ishibashi
S
S
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Nakazawa
M
M
Tawaratani
T
T
Yoshida
M
M
Tamura
H
H
Adachi
T
T
Kawaguchi
K
K
Iwakura
K
K
Sumi
N
N
Wakabayashi
K
K
D000818:Animals; D014453:Glucuronosyltransferase / Q000032:analysis; D008862:Microsomes, Liver / Q000201:enzymology; D010648:Phenylacetates / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014535:Uridine Diphosphate Glucuronic Acid; D014549:Urinary Incontinence / Q000188:drug therapy; D014555:Urination Disorders / Q000188:drug therapy*
D010648:Phenylacetates; D014535:Uridine Diphosphate Glucuronic Acid; D013972:Thyrotropin; C105354:temiverine; D014453:Glucuronosyltransferase; D013974:Thyroxine