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

Isis J. Amaye, Thomas Heinbockel, Julia Woods, Zejun Wang, Miguel Martin-Caraballo and Patrice Jackson-Ayotunde
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Isis J. Amaye: Department of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, One Backbone Road, Princess Anne, MD 21853, USA
Thomas Heinbockel: Department of Anatomy, College of Medicine, Howard University, 520 W Street, NW, Washington, DC 20059, USA
Julia Woods: Department of Anatomy, College of Medicine, Howard University, 520 W Street, NW, Washington, DC 20059, USA
Zejun Wang: Department of Anatomy, College of Medicine, Howard University, 520 W Street, NW, Washington, DC 20059, USA
Miguel Martin-Caraballo: Department of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, One Backbone Road, Princess Anne, MD 21853, USA
Patrice Jackson-Ayotunde: Department of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, One Backbone Road, Princess Anne, MD 21853, USA

IJERPH, 2018, vol. 15, issue 8, 1-13

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.

Keywords: anticonvulsant; brain; calcium channel; drug discovery; epilepsy; enaminones; electrophysiology; GABA; neuron; sodium channel (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2018
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