Ishibashi S, Nishizawa Y, Taniguchi Y, Kikumori M, Nishimori T, Iwakura K, Sumi N
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
J Toxicol Sci. 1995 Dec;20 Suppl 2:237-57. doi: 10.2131/jts.20.supplementii_237.
A repeated dose toxicity study of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was conducted in beagle dogs. Male and female dogs were given the drug intravenously for 26 weeks at doses of 0 (control), 0.02, 0.2, 2 and 20 mg/kg. After discontinuation of the treatment, a 9-week recovery test was also conducted. No deaths related to the treatment were observed. Nasal discharge in all dose groups, and tremor, salivation and emesis in the 0.2 mg/kg group and over were seen. Decrease in body weight gain was observed in the 2 and 20 mg/kg groups. There were no abnormalities in body temperature, and food and water consumptions. Urinalysis and electrocardiographic, ophthalmoscopic and hematologic examinations failed to show any abnormalities attributable to the treatment. In blood chemical examination, increase in T3 level was observed in the 2 and 20 mg/kg groups of females. There were no pathological findings attributable to the treatment. The changes mentioned above were satisfactorily reversible. The nasal discharge seen in the 0.02 mg/kg group was considered to be of no toxicological significance. These results show that the NOAEL of montirelin hydrate is 0.02 mg/kg for 26-week repeated dose toxicity in dogs.
对一种用于治疗意识障碍的新药水合蒙特瑞林（NS - 3）进行了比格犬重复给药毒性研究。雄性和雌性犬静脉注射该药物，持续26周，剂量分别为0（对照）、0.02、0.2、2和20 mg/kg。停药后，还进行了为期9周的恢复试验。未观察到与治疗相关的死亡。所有剂量组均出现鼻分泌物，0.2 mg/kg及以上剂量组出现震颤、流涎和呕吐。2和20 mg/kg组体重增加减少。体温、食物和水消耗量均无异常。尿液分析、心电图、眼科和血液学检查均未显示任何与治疗相关的异常。血液化学检查中，2和20 mg/kg雌性组T3水平升高。未发现与治疗相关的病理结果。上述变化可令人满意地逆转。0.02 mg/kg组出现的鼻分泌物被认为无毒理学意义。这些结果表明，水合蒙特瑞林在犬重复给药26周毒性试验中的无观察到有害作用水平（NOAEL）为0.02 mg/kg。
