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Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits

BACKGROUND: Memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, has been approved for use in Alzheimer’s disease, but an increasing number of studies have investigated its utility for neuropsychiatric disorders. Here, we characterized a novel compound, fluoroethylnormemtantine (FEN...

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Autores principales: Chen, Briana K, Le Pen, Gwenaëlle, Eckmier, Adam, Rubinstenn, Gilles, Jay, Therese M, Denny, Christine A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278800/
https://www.ncbi.nlm.nih.gov/pubmed/33631001
http://dx.doi.org/10.1093/ijnp/pyab007
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author Chen, Briana K
Le Pen, Gwenaëlle
Eckmier, Adam
Rubinstenn, Gilles
Jay, Therese M
Denny, Christine A
author_facet Chen, Briana K
Le Pen, Gwenaëlle
Eckmier, Adam
Rubinstenn, Gilles
Jay, Therese M
Denny, Christine A
author_sort Chen, Briana K
collection PubMed
description BACKGROUND: Memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, has been approved for use in Alzheimer’s disease, but an increasing number of studies have investigated its utility for neuropsychiatric disorders. Here, we characterized a novel compound, fluoroethylnormemtantine (FENM), which was derived from memantine with an extra Fluor in an optimized position for in vivo biomarker labeling. We sought to determine if FENM produced similar behavioral effects as memantine and/or if FENM has beneficial effects against fear, avoidance, and behavioral despair. METHODS: We administered saline, FENM, or memantine prior to a number of behavioral assays, including paired-pulse inhibition, open field, light dark test, forced swim test, and cued fear conditioning in male Wistar rats. RESULTS: Unlike memantine, FENM did not produce nonspecific side effects and did not alter sensorimotor gating or locomotion. FENM decreased immobility in the forced swim test. Moreover, FENM robustly facilitated fear extinction learning when administered prior to either cued fear conditioning training or tone reexposure. CONCLUSIONS: These results suggest that FENM is a promising, novel compound that robustly reduces fear behavior and may be useful for further preclinical testing.
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spelling pubmed-82788002021-07-14 Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits Chen, Briana K Le Pen, Gwenaëlle Eckmier, Adam Rubinstenn, Gilles Jay, Therese M Denny, Christine A Int J Neuropsychopharmacol Regular Research Articles BACKGROUND: Memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, has been approved for use in Alzheimer’s disease, but an increasing number of studies have investigated its utility for neuropsychiatric disorders. Here, we characterized a novel compound, fluoroethylnormemtantine (FENM), which was derived from memantine with an extra Fluor in an optimized position for in vivo biomarker labeling. We sought to determine if FENM produced similar behavioral effects as memantine and/or if FENM has beneficial effects against fear, avoidance, and behavioral despair. METHODS: We administered saline, FENM, or memantine prior to a number of behavioral assays, including paired-pulse inhibition, open field, light dark test, forced swim test, and cued fear conditioning in male Wistar rats. RESULTS: Unlike memantine, FENM did not produce nonspecific side effects and did not alter sensorimotor gating or locomotion. FENM decreased immobility in the forced swim test. Moreover, FENM robustly facilitated fear extinction learning when administered prior to either cued fear conditioning training or tone reexposure. CONCLUSIONS: These results suggest that FENM is a promising, novel compound that robustly reduces fear behavior and may be useful for further preclinical testing. Oxford University Press 2021-02-25 /pmc/articles/PMC8278800/ /pubmed/33631001 http://dx.doi.org/10.1093/ijnp/pyab007 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of CINP. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Regular Research Articles
Chen, Briana K
Le Pen, Gwenaëlle
Eckmier, Adam
Rubinstenn, Gilles
Jay, Therese M
Denny, Christine A
Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits
title Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits
title_full Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits
title_fullStr Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits
title_full_unstemmed Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits
title_short Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits
title_sort fluoroethylnormemantine, a novel derivative of memantine, facilitates extinction learning without sensorimotor deficits
topic Regular Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278800/
https://www.ncbi.nlm.nih.gov/pubmed/33631001
http://dx.doi.org/10.1093/ijnp/pyab007
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