6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity.
6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity.
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DOI：
10.3390/ijerph15081784
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发表时间：
2018-08-20
影响因子：
--
通讯作者：
Jackson-Ayotunde P
中科院分区：
文献类型：
--
作者：
Amaye IJ;Heinbockel T;Woods J;Wang Z;Martin-Caraballo M;Jackson-Ayotunde P
合成了一个新的氟化N-苯甲酰胺烯胺酮的小型库，并在一系列急性临床前癫痫发作模型中进行了评价。三种化合物（GSA 62、TTA 35和WWB 67）在6-Hz“精神病”44-mA啮齿动物模型中被发现具有良好的抗惊厥活性。本研究的重点是阐明活性类似物对肿瘤相关分子靶标的作用模式。采用电生理学研究来评价化合物抑制中枢嗅觉神经元、二尖瓣细胞和感觉样ND 7/23细胞中的神经元活性的能力，所述感觉样ND 7/23细胞表达各种电压和配体门控离子通道。我们没有发现这三种化合物对二尖瓣细胞动作电位产生的任何显着影响。用50 µM GSA 62、TTA 35和WWB 67处理ND 7/23细胞，使全细胞钠电流的幅度显著降低。用这些化合物对ND 7/23细胞进行类似处理对T型钙电流没有影响，表明氟化N-苯甲酰胺烯胺酮类似物可能对电压门控钠通道而不是钙通道具有选择性作用。
A small library of novel fluorinated N-benzamide enaminones were synthesized and evaluated in a battery of acute preclinical seizure models. Three compounds (GSA 62, TTA 35, and WWB 67) were found to have good anticonvulsant activity in the 6-Hz ‘psychomotor’ 44-mA rodent model. The focus of this study was to elucidate the active analogs’ mode of action on seizure-related molecular targets. Electrophysiology studies were employed to evaluate the compounds’ ability to inhibit neuronal activity in central olfactory neurons, mitral cells, and sensory-like ND7/23 cells, which express an assortment of voltage and ligand-gated ion channels. We did not find any significant effects of the three compounds on action potential generation in mitral cells. The treatment of ND7/23 cells with 50 µM of GSA 62, TTA 35, and WWB 67 generated a significant reduction in the amplitude of whole-cell sodium currents. Similar treatment of ND7/23 cells with these compounds had no effect on T-type calcium currents, indicating that fluorinated N-benzamide enaminone analogs may have a selective effect on voltage-gated sodium channels, but not calcium channels.
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影响因子：
2.2
作者：
Barton, ME;Klein, BD;White, HS
通讯作者：
White, HS
影响因子：
6.7
作者：
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影响因子：
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作者：
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通讯作者：
Sharma, Shalini
影响因子：
3.5
作者：
Jackson, Patrice L.;Scott, K. R.;Fang, Ya-Yin
通讯作者：
Fang, Ya-Yin
影响因子：
5.6
作者：
Choi, Hyunmi;Hayat, Matthew J.;Heiman, Gary A.
通讯作者：
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