title: [Single dose toxicity studies of metabolite, degradation product and impurity of montirelin hydrate (NS-3) in mice].
abstract: Montirelin hydrate (NS-3) is a new drug for the treatment of disturbance of consciousness. The single dose toxicity studies of its degradation product and impurity (CNK-603) and its metabolite (CNK-6004) were conducted in Slc: ddY mice. The compounds were administered intravenously to male and female mice. Deaths occurred in both sexes of mice receiving more than 125 mg/kg of CNK-603. There were no treatment-related effects on survival in both sexes of mice receiving doses up to 2,000 mg/kg of CNK-6004. Approximate lethal dose of CNK-603 was 125 mg/kg and lethal dose of CNK-6004 was more than 2,000 mg/kg. Decrease in locomotor activity was observed in mice receiving the two compounds. Tremor, prone position and dyspnea were seen in mice receiving CNK-603. The body weight showed no changes attributable to the dosing of the two compounds in mice. In autopsies, congestion and hemorrhage in the lung were observed in dead mice given CNK-603. There were no remarkable changes in mice given CNK-6004. These results show that the lethal dose of CNK-603 is over 4 times lower than that of montirelin hydrate, and that CNK-6004 is less toxic than montirelin hydrate.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiguchi
authors.forename: M
authors.initials: M
authors.lastname: Nakazawa
authors.forename: T
authors.initials: T
authors.lastname: Oka
authors.forename: Y
authors.initials: Y
authors.lastname: Hagidai
authors.forename: K
authors.initials: K
authors.lastname: Iwakura
authors.forename: N
authors.initials: N
authors.lastname: Sumi
mesh_terms: D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage / Q000633:toxicity*; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D007275:Injections, Intravenous; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D016684:Prone Position; D013329:Structure-Activity Relationship; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D014202:Tremor / Q000139:chemically induced
chemical_list: D004151:Dipeptides; D009025:Morpholines; C031926:montirelin; D013973:Thyrotropin-Releasing Hormone; C102905:CNK 6004