Effects of
MCI-2016 on SMA changes were examined under several experimental conditions (normal conditions,
hypoxia and
head injury). Under normal conditions,
MCI-2016 showed a significant increase of SMA after single administration of 12 mg/kg, i.p. Other doses (12.5-50 mg/kg, p.o. and 3-6 mg/kg, i.p.) of
MCI-2016 were without significant effect. Under the same condition,
MCI-2016 produced a dose-dependent increase of SMA after repeated doses of 12.5 to 50 mg/kg, p.o. (9-10 days administrations). After 5 days repeated administration,
MCI-2016 significantly improved the decreased SMA due to
hypoxia (rats) at 50 to 100 mg/kg, p.o. Furthermore, the
drug also improved the decreased spontaneity due to
head injury (mice) at 50 to 400 mg/kg, p.o. These improving effects of
MCI-2016 were superior to those of Ca-hopantenate. The SMA increasing effect of
MCI-2016 (12 mg/kg, i.p.) was antagonized more strongly by
phenoxybenzamine than by
haloperidol. In addition, the
drug was shown to be rather antagonistic to the effects of
anticholinergic agents. These effects may indicate the existence of qualitative differences between
MCI-2016 and
methamphetamine in the SMA increasing actions. It is also suggested that
MCI-2016 may exhibit the above pharmacological effects through possible activation of noradrenergic and/or
cholinergic mechanisms.