Galantamine potentiates the neuroprotective effect of memantine against NMDA‐induced excitotoxicity
Open accessAbstract
The combination of memantine, an N‐methyl‐d‐aspartate (NMDA) receptor antagonist, with an acetylcholinesterase inhibitor (AChEI) is the current standard of care in A lzheimer's disease (AD). Galantamine, an AChEI currently marketed for the treatment of AD, exerts memory‐enhancing and neuroprotective effects via activation of nicotinic acetylcholine receptors (nAChR s). Here, we investigated the neuroprotective properties of galantamine in primary cultures of rat cortical neurons when given alone or in combination with memantine. In agreement with previous findings, we found that memantine was fully effective in reversing NMDA toxicity at concentrations of 2.5 and 5 μmol/L. Galantamine also completely reversed NMDA toxicity at a concentration of 5 μmol/L. The α7 and α4β2 nAChR antagonists, methyllycaconitine, and dihydro‐β‐erythroidine blocked the neuroprotective effect of galantamine, demonstrating the involvement of nAChR s. The combination of memantine with galantamine produced synergistic actions, such that full neuroprotective efficacy, was obtained at inactive concentrations of memantine (0.1 μmol/L) and galantamine (1 μmol/L). A similar potentiation was also observed when memantine was replaced with ifenprodil, suggesting a possible involvement of the NR 2B subunit of the NMDA receptor. In summary, our study reports for the first time at a cellular level that memantine and galantamine interact on the same excitotoxic cascade and that the combination of these two drugs can result in a remarkable neuroprotective effect.
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The combination of memantine (2) and galantamine (10) resulted in a significant synergistic effect, even at subactive concentrations.
“In the latter case, they resulted in a significant synergistic effect, even at subactive concentrations.112”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [112]
Memantine (2) and galantamine (10) were able to reverse NMDA toxicity alone or in combination.
“This study showed how the two drugs were able to reverse NMDA toxicity alone or in combination.”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [112]
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- Authors
- Lopes, J. P., Tarozzo, G., Reggiani, A., Piomelli, D., & Cavalli, A.
- Affiliations
- Italian Institute of Technology (IT)
- University of California, Irvine (US)
- Corresponding author
- Cavalli, Andrea
- Venue
- Brain and Behavior
- Publisher
- Wiley
- Published
- 2013-01-11
- Volume
- 3
- Issue
- 2
- Pages
- 67-74
- ISSN
- 2157-9032 (ISSN-L)
- 2162-3279
- PMC
- PMC3607148
- OpenAlex
- W2016205566
- Cited by
- 64
- References
- 33
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 9 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 3 · 2013: 1
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain and Behavior (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- galantamine, memantine, NMDA receptor antagonism, excitotoxicity, neuroprotection, nicotinic acetylcholine receptors, acetylcholinesterase inhibitors, Alzheimer's disease, drug synergy, ifenprodil, NR2B subunit, cortical neurons, methyllycaconitine, dihydro-beta-erythroidine
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