6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity

被引：25

作者：

Amaye, Isis J. ^{[1
]}

Heinbockel, Thomas ^{[2
]}

Woods, Julia ^{[2
]}

Wang, Zejun ^{[2
]}

Martin-Caraballo, Miguel ^{[1
]}

Jackson-Ayotunde, Patrice ^{[1
]}

机构：

[1] Univ Maryland Eastern Shore, Sch Pharm & Hlth Profess, Dept Pharmaceut Sci, One Backbone Rd, Princess Anne, MD 21853 USA

[2] Howard Univ, Dept Anat, Coll Med, 520 W St NW, Washington, DC 20059 USA

来源：

INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH | 2018年 / 15卷 / 08期

基金：

美国国家科学基金会;

关键词：

anticonvulsant; brain; calcium channel; drug discovery; epilepsy; enaminones; electrophysiology; GABA; neuron; sodium channel; SUBSTITUTED VINYLIC BENZAMIDES; EPILEPSY; PROGRAM;

D O I：

10.3390/ijerph15081784

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

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 mu M 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.

引用

页数：13

共 22 条

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