1-(p-Chlorophenylsulfonyl)-2-imidazolidinone(CPSI)の血糖上昇機作について

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概要

• 論文の詳細を見る

• It was reported previously that hypoglycemic sulfonylureas turned into hyperglycemic when a cyclized urea structure was involved in their molecules. The mechanism of the hyperglycemic action of 1-(p-chlorophenylsulfonyl)-2-imidazolidinone (CPSI), a derivative of chlorpropamide (P-607), was compared with the hypoglycemic action of the parent P-607,and the results obtained were summarized as follows. 1) An enhanced blood sugar level in rabbits induced by CPSI administration (100 mg/kg, p.o.) was decreased transiently by insulin (0.2 IU/kg, i.v.) and consistently by P-607 (100 mg/kg, p.o.). 2) An ora1 administration of P-607 (100 mg/kg) to the hyperglycemized rabbits treated with CPSI (100 mg/kg, p.o.), resulted in a rapid and transient increase of the peripheric blood insulin level, followed by a rapid decrease of blood glucose. In contrast, these phenomena were not observed when animals were not pretreated with CPSI. 3) Pretreatment of rats with CPSI (100 mg/kg, p.o.) inhibited the increase of periphericblood insulin level induced by glucose administration (2400 mg/kg, p.o.). 4) An oral administration of a relatively large quantities of CPSI (300 mg/kg) to rats, resulted in a more prolonged low peripheric blood insulin level, followed by a marked increase of pancreas insulin and the hyperglycemic state was observed. In contrast, when P-607 (300 mg/kg, p.o.) was administered, a transient and a marked increase of peripheric blood insulin level together with a decrease of pancreas insulin, was observed and a lasting hypoglycemic state was induced. 5) When rats were dosed orally for four consecutive weeks with CPSI (100 mg/kg daily), the hyperglycemic phenomenon was constantly reproduced during the whole experimental period. No histopathological abnormalities were noticed on the pancreas Langerhan's island. It was concluded that unlike alloxan, the hyperglycemic action of CPSI might be induced by its inhibitory effect on the process of insulin release from pancreatic β cells.

• 公益社団法人日本薬学会の論文
• 1975-07-25

著者

• 山田 澄

  北陸大学薬学部

• 山田 澄

  神戸女子薬科大学

• 中西 一之

  神戸女子薬科大学

• 寺田 護

  神戸女子薬科大学

• 巻幡 希子

  神戸女子薬科大学

• 秦 雅子

  神戸女子薬科大学

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