Effects of NIK-247 on CO-induced impairment of passive avoidance in mice.
The effect of NIK-247 on carbon monoxide (CO)-induced amnesia were investigated. A step-down type passive avoidance task with mice was used to compare the effects of NIK-247 with those of tacrine. Two types of CO-induced amnesia model, acute and delayed models, were used. The acute amnesia model was developed using mice exposed to CO before memory consolidation, just after training, and a retention test carried out 24 h after training. The delayed amnesia model was prepared 7 days after CO exposure even when the animals were exposed to CO 4 h after training, after memory had consolidated. NIK-247 administered post-training at 0.03-0.3 and 3 mg/kg or pre-retention test (24 h after training) at 0.3 and 10 mg/kg attenuated the acute amnesia. In addition, NIK-247 (0.03, 0.1, 1 and 10 mg/kg) and tacrine (0.03, 0.1 and 1 mg/kg) administered before the retention test (7 days after CO exposure) improved retrieval in the delayed amnesia model. Tacrine (0.01-0.3 and 3 mg/kg), administered post-training, attenuated the acute amnesia but pre-retention test administration did not. The dose-response curves for NIK-247 and tacrine were biphasic bell-shaped. These results indicated that NIK-247 has an improving effect on hypoxia-induced acute and delayed cognitive dysfunction, and suggest that NIK-247 has promise as a nootropic drug for therapy of memory deficits in patients with cerebrovascular-type dementing disorders.
Yoshida
S
S
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Nabeshima
T
T
Kinbara
K
K
Kameyama
T
T
D000634:Aminoquinolines / Q000494:pharmacology*; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002248:Carbon Monoxide / Q000633:toxicity*; D002800:Cholinesterase Inhibitors; D008297:Male; D051379:Mice; D011619:Psychotropic Drugs / Q000494:pharmacology; D013619:Tacrine / Q000494:pharmacology; D013997:Time Factors
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D011619:Psychotropic Drugs; D013619:Tacrine; D002248:Carbon Monoxide; C049860:amiridine