Studies on wakefulness-promoting effect of memantine in rats.
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.
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1 Tsushima-Naka, Kita-Ku, 700-8530, Okayama, Japan.
Takayuki
T
Ishida
Yoshihito
Y
Obara
Chiaki
C
Kamei
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D008774:Methylphenidate / Q000494:pharmacology; D017286:Polysomnography; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D012892:Sleep Deprivation; D012894:Sleep Stages; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; C534628:SCH 23390; D008774:Methylphenidate; D020891:Raclopride; D008559:Memantine