Studies on wakefulness-promoting effect of memantine in rats
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Updated: Jun 20, 2026
Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Takayuki Ishida1, Yoshihito Obara, Chiaki Kamei
1Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1 Tsushima-Naka, Kita-Ku, 700-8530, Okayama, Japan.
Abstract:
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.
Insights
Memantine, an anti-dementia drug, effectively reduces excessive daytime sleepiness by increasing wakefulness after sleep deprivation. Its wakefulness-promoting effects involve the D1 dopamine receptor, similar to methylphenidate.
Area of Science:
- Neuroscience
- Pharmacology
- Sleep Medicine
Background:
- Excessive daytime sleepiness is a debilitating condition impacting quality of life.
- Current treatments for sleepiness have limitations, necessitating novel therapeutic approaches.
- Memantine, an NMDA receptor antagonist used for Alzheimer's disease, has a potential, unexplored role in managing sleep disorders.
Purpose of the Study:
- To investigate the efficacy of memantine in treating excessive daytime sleepiness following sleep deprivation.
- To compare memantine's effects with methylphenidate, a known wakefulness-promoting agent.
- To elucidate the role of the dopaminergic system, specifically D1 and D2 receptors, in memantine's wakefulness-promoting action.
Main Methods:
- Adult male rats underwent chronic implantation of electroencephalogram (EEG) and electromyogram (EMG) electrodes.
- EEG and EMG were recorded to assess sleep-wake patterns after a 6-hour sleep deprivation period.
- Rats were administered varying doses of memantine or methylphenidate, with or without dopamine receptor antagonists (SCH 23390 for D1, raclopride for D2).
Main Results:
- Both memantine and methylphenidate significantly increased sleep latency and total awake time in sleep-deprived rats.
- Administration of memantine and methylphenidate led to significant reductions in non-rapid eye movement (NREM) and REM sleep durations.
- The wakefulness-promoting effect of memantine was significantly attenuated by the D1 receptor antagonist SCH 23390, but not by the D2 receptor antagonist raclopride.
Conclusions:
- Memantine demonstrates a comparable efficacy to methylphenidate in alleviating excessive sleepiness induced by sleep deprivation.
- The findings suggest that the wakefulness-promoting effects of memantine are mediated, at least in part, through the D1 dopamine receptor.
- Memantine represents a potential therapeutic candidate for managing excessive daytime sleepiness, warranting further clinical investigation.
