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Int. J. Environ. Res. Public Health 2018, 15(8), 1784; https://doi.org/10.3390/ijerph15081784

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

1
Department of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, One Backbone Road, Princess Anne, MD 21853, USA
2
Department of Anatomy, College of Medicine, Howard University, 520 W Street, NW, Washington, DC 20059, USA
*
Author to whom correspondence should be addressed.
Received: 15 July 2018 / Revised: 6 August 2018 / Accepted: 8 August 2018 / Published: 20 August 2018
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Abstract

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. View Full-Text
Keywords: anticonvulsant; brain; calcium channel; drug discovery; epilepsy; enaminones; electrophysiology; GABA; neuron; sodium channel anticonvulsant; brain; calcium channel; drug discovery; epilepsy; enaminones; electrophysiology; GABA; neuron; sodium channel
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Amaye, I.J.; Heinbockel, T.; Woods, J.; Wang, Z.; Martin-Caraballo, M.; Jackson-Ayotunde, P. 6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity. Int. J. Environ. Res. Public Health 2018, 15, 1784.

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