Kikumori M, Nishida I, Kojima M, Taniguchi Y, Yasuhira K, Ishibashi S, Iwakura K, Sumi N
Environmental Biological Life Science Research Center Inc., Shiga, Japan.
J Toxicol Sci. 1995 Dec;20 Suppl 2:171-89. doi: 10.2131/jts.20.supplementii_171.
A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in Sprague-Dawley rats. Male and female rats were given the drug intravenously for 5 weeks at doses of 0 (control), 0.05, 0.5, 5 and 50 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted in the 0, 0.5 and 50 mg/kg groups. No deaths related to the treatment were observed. Tremor was seen in the 50 mg/kg group. Polyuria was observed in the 5 and 50 mg/kg groups. There were decreases in body weight gain in the 0.5 mg/kg group and over of males, and in food consumption in all male dose groups and increase in water consumption in the 5 and 50 mg/kg groups. In blood chemical examination, decrease in triglyceride was observed in the 5 and 50 mg/kg groups of males. Urinalysis showed increase in urine volume in the 0.5 mg/kg group and over. Ophthalmoscopic and hematologic examinations failed to show any abnormalities attributable to the treatment. Pathological examination disclosed serous cell hypertrophy of the submandibular gland in all dose groups and increase in its organ weight in the 0.5 mg/kg group and over. The changes mentioned above were satisfactorily reversible except for the serous cell hypertrophy of the submandibular gland in the 50 mg/kg group. The decrease in food consumption and serous cell hypertrophy of the submandibular gland in the 0.05 mg/kg group were considered to be of no toxicological significance. These results show that the NOAEL of montirelin hydrate is 0.05 mg/kg for 5-week repeated dose toxicity in rats.
对一种用于治疗意识障碍的新药水合蒙特瑞林（NS - 3）进行了重复剂量毒性研究，实验对象为Sprague - Dawley大鼠。雄性和雌性大鼠静脉注射该药物，持续5周，剂量分别为0（对照组）、0.05、0.5、5和50mg/kg。治疗结束后，还对0、0.5和50mg/kg组进行了为期4周的恢复试验。未观察到与治疗相关的死亡情况。在50mg/kg组中观察到震颤。在5和50mg/kg组中观察到多尿。0.5mg/kg组及以上剂量组的雄性大鼠体重增加减少，所有雄性剂量组的食物摄入量减少，5和50mg/kg组的水摄入量增加。血液化学检查显示，5和50mg/kg组的雄性大鼠甘油三酯降低。尿液分析显示，0.5mg/kg组及以上剂量组尿量增加。眼科和血液学检查未发现任何与治疗相关的异常。病理检查发现，所有剂量组的下颌下腺浆液细胞肥大，0.5mg/kg组及以上剂量组的下颌下腺器官重量增加。除50mg/kg组下颌下腺浆液细胞肥大外，上述变化均可满意地逆转。0.05mg/kg组食物摄入量减少和下颌下腺浆液细胞肥大被认为无毒理学意义。这些结果表明，水合蒙特瑞林对大鼠5周重复剂量毒性的无观察到有害作用水平为0.05mg/kg。
