Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer’s disease
Open accessAbstract
Alzheimer's disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over-activation of N-methyl-D-aspartate (NMDA) receptors, amyloid β (Aβ) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN-08, a novel memantine nitrate, was found to inhibit Aβ accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice (for a 6-month preventative course) and in the 8-month-old triple-transgenic (3×Tg-AD) mice (for a 4-month therapeutic course). In vitro, MN-08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3β pathway, subsequently preventing glutamate-induced neuronal loss. In addition, MN-08 had favorable pharmacokinetics, blood-brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD.
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Memantine is safe and well-tolerated and is used to treat moderate-to-severe AD alone or in combination with AChEI.
“Memantine is safe and well-tolerated; it is used to treat moderate-to-severe AD alone or in combination with AChEI [124,125,126].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [126]
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Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56 · see citing works
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BackgroundTurcu, A. L., Companys-Alemany, J., Phillips, M. B., Patel, D. S., Griñán-Ferré, C., Loza, M. I., Brea, J. M., Pérez, B., Soto, D., Sureda, F. X., et al. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114354 · Cited by 27 · see citing works
- Authors
- Wu, L., Zhou, X., Cao, Y., MAK, S. H., Zha, L., Li, N., Su, Z., Han, Y., Wang, Y., Man Hoi, M. P., Sun, Y., Zhang, G., Zhang, Z., & Yang, X.
- Affiliations
- Jinan University (CN)
- Department of Applied Biology and Chemical Technology Institute of Modern Chinese Medicine The Hong Kong Polytechnic University Hong Kong China
- Hong Kong Polytechnic University (HK)
- State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences University of Macau Macau China
- Shenzhen Center for Disease Control and Prevention (CN)
- Corresponding author
- Zhang, Gaoxiao
- Zhang, Zaijun
- Yang, Xifei
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2021-05-06
- Volume
- 20
- Issue
- 6
- Pages
- e13371-e13371
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC8208785
- OpenAlex
- W3157883200
- Cited by
- 24
- References
- 39
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 1
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PolyU Institutional Research Archive (Hong Kong Polytechnic University) (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (NSFC 82061160374)
- China Postdoctoral Science Foundation (2020M683207)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, NMDA receptor antagonism, amyloid-beta deposition, APP/PS1 mice, 3xTg-AD mice, cognitive impairment, dendritic spine loss, ERK signaling, PI3K/AKT/GSK3β pathway, calcium influx, blood-brain barrier penetration, pharmacokinetics, drug safety
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Memantine, Mice, Transgenic, Mice
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