[Single dose toxicity studies of montirelin hydrate(NS-3) in mice, rats and dogs].
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.
Kikumori
M
M
Environmental Biological Life Science Research Center Inc., Shiga, Japan.
Nishida
I
I
Nishimura
T
T
Yasuhira
K
K
Nakai
N
N
Nishiguchi
Y
Y
Iwakura
K
K
Nagasawa
H
H
Sumi
N
N
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D014202:Tremor / Q000139:chemically induced
C031926:montirelin; D013973:Thyrotropin-Releasing Hormone