To predict the possible activity on
memory disorders, the effect of
MCI-2016 was compared with those of
physostigmine,
choline chloride,
methamphetamine,
apomorphine,
imipramine and
calcium hopantenate by applying
scopolamine-induced deficit of spontaneous alternation behavior (
scopolamine-SA) as a proposed animal model for
senile dementia.
MCI-2016 was shown to improve the
scopolamine-SA at doses of 25 to 100 mg/kg p.o. without producing any remarkable behavioral abnormalities. As for the effect of reference drugs, two types of
cholinomimetic drugs (
physostigmine and
choline chloride) and
methamphetamine were shown to be active. In the cases of
physostigmine and
methamphetamine, however, behavioral abnormalities were observed at those dose levels effective on
scopolamine-SA. MIC-2016 potentiated the effect of
physostigmine on
scopolamine SA at non active doses of 10 to 20 mg/kg p.o. In comparison with the deleterious effect of
scopolamine on spontaneous alternation (SA) behavior itself, none of the test drugs except for
imipramine were shown to disrupt the SA. Considering the disruptive or improving actions of various agents on SA or
scopolamine-SA, it may be suggested that the present model is relatively sensitive to those drugs which affect the
cholinergic mechanism either directly or indirectly. Mechanisms of the actions of
MCI-2016 and
methamphetamine were also discussed with reference to possible involvement of
cholinergic mechanisms.