[Twenty-six-week intravenous toxicity study of montirelin hydrate (NS-3) in dogs followed by 9-week recovery test].

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.