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新型抗高血压药物胍那苄的生殖研究(4)——家兔致畸试验

[Reproduction study of Guanabenz, a new antihypertensive agent (4) - teratological test in rabbits].

作者信息

Akatsuka K, Hashimoto T, Takeuchi K, Kogure M

出版信息

J Toxicol Sci. 1982 Dec;7 Suppl 2:141-50. doi: 10.2131/jts.7.supplementii_141.

Abstract

Guanabenz (WY-8678) was given to pregnant rabbits to examine its effects on the dams and their fetuses. The drug was administered orally to rabbits at does of 10, 8, 5 and 1 mg/kg/day from the 6th to 18th days of gestation. The vehicle used was 5%-Arabic Gum at dose level of 10 ml/kg, and a control experiment where only the vehicle was administered was also conducted. The results obtained were as follows. 1. Concerning the effects on the dams, the symptoms of decrease in spontaneous movement and sedation were observed at 10 mg/kg. However, mean body weight, food consumption, and organ weight were not influenced by Guanabenz. 2. In the observation of the fetuses, no difference was observed among groups in the number of corpora lutea, the number of implantations, implantation rate, the number of resorption, the number of dead fetuses, the number of live fetuses, sex ratio, mean body weight of the fetuses, mean body length of the fetuses, and mean placenta weight of the fetuses. 3. No difference was observed among groups regarding external malformations, visceral malformations, skeletal malformations, skeletal variations and degree of ossification in the fetuses. From these results, it is concluded that Guanabenz has no teratogenic potential in pregnant rabbits and on effect no fetuses at doses of 8 mg/kg or lower.

摘要

给予孕兔胍那苄(WY - 8678)以检查其对母兔及其胎儿的影响。在妊娠第6至18天,以10、8、5和1毫克/千克/天的剂量对兔口服该药物。所用赋形剂为5%阿拉伯胶,剂量为10毫升/千克,同时还进行了仅给予赋形剂的对照实验。得到的结果如下:1. 关于对母兔的影响,在10毫克/千克剂量时观察到自发活动减少和镇静的症状。然而,胍那苄对平均体重、食物消耗量和器官重量没有影响。2. 在观察胎儿时,各组在黄体数量、着床数、着床率、吸收数、死胎数、活胎数、性别比、胎儿平均体重、胎儿平均体长和胎儿平均胎盘重量方面没有差异。3. 在胎儿的外部畸形、内脏畸形、骨骼畸形、骨骼变异和骨化程度方面,各组之间没有差异。从这些结果可以得出结论,胍那苄在孕兔中没有致畸潜力,在8毫克/千克或更低剂量下对胎儿没有影响。

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