Kikumori M, Nishida I, Nishimura T, Yasuhira K, Nakai N, Nishiguchi Y, Iwakura K, Nagasawa H, Sumi N
Environmental Biological Life Science Research Center Inc., Shiga, Japan.
J Toxicol Sci. 1995 Dec;20 Suppl 2:153-63. doi: 10.2131/jts.20.supplementii_153.
The single dose toxicity studies of montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, were conducted in Slc:ddY mice, Slc:SD rats, and beagle dogs of both sexes. The drug was administered intravenously (i.v.) to mice, rats and dogs, and intramuscularly (i.m.) to mice and rats. The animals were observed for 14 days after administration. LD50 values were more than 500 mg/kg and 200 mg/kg in mice and rats, respectively, by the i.v. route, and more than 20 mg/kg in both animal species by the i.m. route. In dogs, the minimum lethal dose was more than 200 mg/kg by the i.v. route. Mice that received more than 125 mg/kg by the i.v. route showed tremor and a decrease in locomotor activity during administration and for 30 min thereafter. Mice that received more than 5 mg/kg by the i.m. route showed tremor 5 min after administration and for 2 hr thereafter. Rats that received more than 50 mg/kg by the i.v. route showed tremor, and those that received 200 mg/kg by the same route showed a decrease in locomotor activity and ataxic gait, during and immediately after administration. Rats that received more than 5 mg/kg by the i.m. route showed tremor, and those that received 20 mg/kg by the same route showed salivation 5 min after administration and for 30 min thereafter. Dogs that received more than 12.5 mg/kg by the i.v. route revealed excitement, biting, vocalization, mydriasis, salivation, urination, defecation, licking chops, vomiting, increase in heart rate, panting, hyperthermia, tremor and conjunctival injection during administration and for 6 hr thereafter. The body weight, food consumption and water consumption, and pathological findings showed no changes attributable to the dosing of montirelin hydrate in any animal.
对用于治疗意识障碍的新药水合蒙特瑞林（NS - 3）进行了单剂量毒性研究，实验对象为Slc:ddY小鼠、Slc:SD大鼠以及雌雄比格犬。药物通过静脉注射（i.v.）给予小鼠、大鼠和犬，通过肌肉注射（i.m.）给予小鼠和大鼠。给药后对动物观察14天。静脉注射途径下，小鼠和大鼠的半数致死量（LD50）分别大于500mg/kg和200mg/kg，肌肉注射途径下两种动物的LD50均大于20mg/kg。对于犬，静脉注射途径下最小致死量大于200mg/kg。静脉注射剂量超过125mg/kg的小鼠在给药期间及之后30分钟出现震颤和运动活性降低。肌肉注射剂量超过5mg/kg的小鼠在给药后5分钟出现震颤，并持续2小时。静脉注射剂量超过50mg/kg的大鼠出现震颤，静脉注射剂量为200mg/kg的大鼠在给药期间及给药后立即出现运动活性降低和共济失调步态。肌肉注射剂量超过5mg/kg的大鼠出现震颤，肌肉注射剂量为20mg/kg的大鼠在给药后5分钟出现流涎，并持续30分钟。静脉注射剂量超过12.5mg/kg的犬在给药期间及之后6小时出现兴奋、咬、叫、瞳孔散大、流涎、排尿、排便、舔嘴、呕吐、心率加快、喘气、体温过高、震颤和结膜充血。在任何动物中，体重、食物摄入量、饮水量以及病理检查结果均未显示出与水合蒙特瑞林给药相关的变化。
