Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits.
Fluoroethylnormemantine, A Novel Derivative of Memantine, Facilitates Extinction Learning Without Sensorimotor Deficits.
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DOI：
10.1093/ijnp/pyab007
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发表时间：
2021-07-14
期刊：
影响因子：
--
通讯作者：
Denny CA
中科院分区：
文献类型：
--
作者：
Chen BK;Le Pen G;Eckmier A;Rubinstenn G;Jay TM;Denny CA
美金刚是一种非竞争性的n -甲基- d -天冬氨酸受体拮抗剂，已被批准用于阿尔茨海默病，但越来越多的研究调查了它对神经精神疾病的效用。在这里，我们鉴定了一种新的化合物，氟乙基正美刚（FENM），它是从美金刚衍生出来的，在体内生物标志物标记的优化位置上有一个额外的氟。我们试图确定FENM是否产生与美金刚相似的行为效果和/或FENM是否对恐惧、逃避和行为绝望有有益的效果。在对雄性Wistar大鼠进行配对脉冲抑制、野外、明暗试验、强迫游泳试验和暗示恐惧条件反射等一系列行为试验之前，我们给药生理盐水、FENM或美金刚。与美金刚不同，FENM不会产生非特异性副作用，也不会改变感觉运动门控或运动。FENM在强迫游泳试验中降低了不动性。此外，在提示恐惧条件反射训练或音调再暴露之前，FENM强有力地促进了恐惧消退学习。这些结果表明，FENM是一种有前景的新型化合物，可以有效地减少恐惧行为，并可能用于进一步的临床前测试。
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. 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. 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. 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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影响因子：
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作者：
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