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.