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Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity
João P Lopes, Glauco Tarozzo, Angelo Reggiani, Daniele Piomelli, Andrea Cavalli. Brain and behavior, 2013-01-11
Topic: Gut, metabolism and diet
The combination of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, with an acetylcholinesterase inhibitor (AChEI) is the current standard of care in Alzheimer'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 (nAChRs). 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 nAChRs. 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 NR2B 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.
Key findings
- 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.
- 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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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 21 of the 56 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain and behavior) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23532860) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 21 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 21 of the 56 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Lopes, J. P., Tarozzo, G., Reggiani, A., Piomelli, D., & Cavalli, A. (2013). Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity. Brain and behavior. https://doi.org/10.1002/brb3.118
Vancouver
Lopes JP, Tarozzo G, Reggiani A, Piomelli D, Cavalli A. Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity. Brain and behavior. 2013. doi:10.1002/brb3.118. PMID: 23532860.
BibTeX
@article{lopes2013-23532860,
author = {Lopes, João P and Tarozzo, Glauco and Reggiani, Angelo and Piomelli, Daniele and Cavalli, Andrea},
title = {{Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity}},
journal = {Brain and behavior},
year = {2013},
doi = {10.1002/brb3.118},
pmid = {23532860},
url = {https://doi.org/10.1002/brb3.118}
}
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