Fluoroethylnormemantine, a novel derivative of memantine, facilitates extinction learning without sensorimotor deficits.

BACKGROUND Memantine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been approved for use in Alzheimer's disease (AD), but increasing 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 (PPI), open field (OF), light dark test (LDT), forced swim test (FST), and cued fear conditioning (FC) 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 FST. Moreover, FENM robustly facilitated fear extinction learning when administered prior to either cued FC training or tone re-exposure. CONCLUSIONS These results suggest that FENM is a promising, novel compound that robustly reduces fear behavior and may be useful for further preclinical testing.