To further predict the possible activity on
memory disorders, the effect of
MCI-2016 (
bifemelane hydrochloride) was examined using the passive avoidance (PAR) failure technique as an experimental model of
amnesia. The
amnesia was produced either by post training treatments of electroconvulsive shock (ECS),
scopolamine (mice) and
cycloheximide or by pre-test injection of
scopolamine (rats). In ECS-PAR failure model, the retention test was carried out 3 hr (3 hr experiment) or 24 hr (24 hr experiment) after ECS.
MCI-2016 showed a significant improvement when administered just after ECS (3 hr experiment, 30 mg/kg, i.p.) or 0.5 hr before the retention test (24 hr experiment, 10-30 mg/kg, i.p.). Cahopantenate was only active in the 3 hr experiment (500 mg/kg, i.p.), and
piracetam was rather active in the 24 hr experiment (60 mg/kg, i.p.).
MCI-2016 (30 mg/kg, i.p.) prevented the
scopolamine-induced PAR-failure. In this model,
physostigmine (0.3 mg/kg, i.p.) exhibited a tendency to improve the failure. In another
scopolamine-induced PAR failure model in mice, all of the test drugs showed a significant improvement at different dose levels. The effect of
MCI-2016 (25-100 mg/kg, p.o.) was superior to those of
piracetam,
aniracetam and
choline chloride. Higher doses of
MCI-2016 were required to improve the
cycloheximide-induced PAR failure. Considering the experimental conditions and results, it may be suggested that
MCI-2016 ameliorates the
amnesia possibly through its influence on memory consolidation and retrieval processes.