We hypothesized that
memantine, an anti-
dementia drug, may be useful for the treatment of
excessive daytime sleepiness. The effect of
memantine on excessive
sleepiness after 6 h
sleep deprivation was studied in comparison with that of
methylphenidate, and the involvement of the dopaminergic system in the wakefulness-promoting effect of
memantine was also evaluated.
Electrodes for electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and dorsal neck muscle, respectively, of adult male rats. EEG and EMG were recorded with an electroencephalograph for 6 h (19:00-01:00). After
sleep deprivation (13:00-19:00), compensatory excessive
sleepiness (19:00-01:00) was observed in rats.
Memantine (10 mg/kg, p.o.) and
methylphenidate (10-30 mg/kg, p.o.) caused a significant increase of sleep latency compared with the control group. Furthermore, a significant increase in total awake time and significant decreases in total non-rapid eye movement (NREM) sleep and REM sleep times were observed by administration of
memantine (3-10 mg/kg) and
methylphenidate (3-30 mg/kg) compared with control in
sleep deprivation rats. Although the effect of
memantine was significantly suppressed by D1 receptor antagonist
SCH 23390 (0.1 mg/kg, i.p.), D2 receptor antagonist
raclopride had no antagonistic effect (1 mg/kg, i.p.). From these results, the effect of
memantine on
sleepiness after
sleep deprivation was similar to that of
methylphenidate, and D1 receptor may be involved in the effect of
memantine.