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[Effects of Yokukansankachimpihange on Memantine-induced Dizziness in Mice with Memory Impairment]
Taiki Shimoyama1, Yayoi Aoki1, Marisa Kaneda1
1Kampo Research Laboratories, Kracie Pharma, Ltd.
Abstract:
Memantine (Mem) is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease. However, side effects, including dizziness, headache and confusion, have been reported. Therefore, although it reduces the symptoms of dementia, such as memory loss, its use is limited by side effects for patients at risk of injury. In the present study, we investigated the effects of the Japanese Kampo medicine yokukansankachimpihange (YKSCH) on Mem-induced dizziness in a mouse model of memory impairment. Mem (20 mg/kg B.W., p.o.) reduced the performance score during the beam balance test and walking time on a rotarod, confirming the disrupted sense of balance and motor coordination. In contrast, YKSCH (750 mg/kg B.W., p.o.) significantly suppressed this disruption of balance and motor coordination in mice. Moreover, YKSCH did not attenuate the ameliorative effects of Mem on learning and memory impairment in the Y-maze test or step-through passive avoidance task. Spatial learning and memory significantly recovered in the Mem-treated group and Mem plus YKSCH-treated group, suggesting no pharmacological interaction between Mem and YKSCH in mice. Therefore, YKSCH may be effective at alleviating the Mem-induced equilibrium disturbance in mice with memory impairment without reducing its memory disorder improvement effects. Our study may be useful for future studies on the combined use of Mem and YKSCH in the treatment of Alzheimer's disease.
Insights
Yokukansankachimpihange (YKSCH) may alleviate memantine-induced dizziness in Alzheimer's disease models. This Japanese Kampo medicine improved motor coordination without affecting memantine's cognitive benefits.
Area of Science:
- Neuroscience
- Pharmacology
- Traditional Japanese Medicine
Background:
- Memantine (Mem), an NMDA receptor antagonist, treats Alzheimer's disease but causes side effects like dizziness, limiting its use.
- Investigating complementary therapies to mitigate memantine's side effects is crucial for patient safety and treatment efficacy.
Purpose of the Study:
- To evaluate the efficacy of the Japanese Kampo medicine yokukansankachimpihange (YKSCH) in reducing memantine-induced dizziness and motor coordination impairment in a mouse model.
- To determine if YKSCH interferes with the cognitive benefits of memantine in treating memory impairment.
Main Methods:
- A mouse model of memory impairment was used to assess the effects of memantine (20 mg/kg) and YKSCH (750 mg/kg) on balance and motor coordination.
- Tests included the beam balance test and rotarod test to evaluate equilibrium and coordination.
- Cognitive function was assessed using the Y-maze and step-through passive avoidance tasks to evaluate learning and memory.
Main Results:
- Memantine administration significantly disrupted balance and motor coordination in mice, as evidenced by reduced performance in balance and rotarod tests.
- YKSCH treatment significantly suppressed these memantine-induced motor impairments.
- YKSCH did not attenuate the positive effects of memantine on spatial learning and memory in the Y-maze and passive avoidance tasks, indicating no pharmacological interaction.
Conclusions:
- Yokukansankachimpihange (YKSCH) may be an effective adjunct therapy for alleviating memantine-induced equilibrium disturbances in patients with memory impairment.
- YKSCH offers a potential strategy to improve the tolerability of memantine treatment for Alzheimer's disease without compromising its therapeutic benefits on cognition.
- Further research into the combined use of memantine and YKSCH is warranted for Alzheimer's disease treatment.
