Morinaga T, Fujii S, Kikumori M, Nishimori T, Watanabe M, Sumi N
Environmental Biological Life Science Research Center Inc., Shiga, Japan.
J Toxicol Sci. 1995 Dec;20 Suppl 2:309-23. doi: 10.2131/jts.20.supplementii_309.
A study of the effect of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, during the perinatal and lactation periods was conducted in Sprague-Dawley rats. Female rats were given the drug intravenously at dose levels of 0 (control), 0.02, 1 and 50 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. In the 1 and 50 mg/kg groups, food and water consumptions decreased after delivery and the weights of adrenals of the dams increased. In addition, tremor, disappeared within some minutes, was observed during administration period in all dams given 50 mg/kg. Moreover, body weight gain was suppressed after delivery, and the weights of submaxillary glands increased, and the weights of thymus and liver decreased in the dams given 50 mg/kg. The drug did not affect delivery. The drug did not have any adverse effects on the newborn including the number of live newborns, birth index and body weights of live newborn. In the 1 or 50 mg/kg group, body weight gains were suppressed and food consumption decreased in the offspring. The drug did not have any adverse effects on the postnatal development of the offspring such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. These results show that the NOAEL of montirelin hydrate are 0.02 mg/kg for general toxicity in mother animals, 50 mg/kg for reproductive function in mother animals and 0.02 mg/kg for their offspring.
在斯普拉格-道利大鼠中进行了一项关于水合蒙特瑞林（NS-3）（一种用于治疗意识障碍的新药）在围产期和哺乳期作用的研究。从妊娠第17天到产后第21天，给雌性大鼠静脉注射剂量水平为0（对照）、0.02、1和50mg/kg的药物。所有怀孕大鼠均自然分娩，以便对其后代进行产后检查。在1mg/kg和50mg/kg组中，产后食物和水的消耗量减少，母鼠肾上腺重量增加。此外，所有给予50mg/kg的母鼠在给药期间均观察到震颤，数分钟内消失。而且，给予50mg/kg的母鼠产后体重增加受到抑制，颌下腺重量增加，胸腺和肝脏重量减轻。该药物不影响分娩。该药物对新生仔鼠没有任何不良影响，包括活产新生仔鼠的数量、出生指数和活产新生仔鼠的体重。在1mg/kg或50mg/kg组中，后代的体重增加受到抑制，食物消耗量减少。该药物对后代的产后发育没有任何不良影响，如分化、功能发育、情绪、运动能力、学习能力或生殖性能。这些结果表明，水合蒙特瑞林的无观察到有害作用水平对于母动物的一般毒性为0.02mg/kg，对于母动物的生殖功能为50mg/kg，对于其后代为0.02mg/kg。
