6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity
AbstractA 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
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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.
Amaye IJ, 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. International Journal of Environmental Research and Public Health. 2018; 15(8):1784.Chicago/Turabian Style
Amaye, Isis J.; Heinbockel, Thomas; Woods, Julia; Wang, Zejun; Martin-Caraballo, Miguel; Jackson-Ayotunde, Patrice. 2018. "6 Hz Active Anticonvulsant Fluorinated N-Benzamide Enaminones and Their Inhibitory Neuronal Activity." Int. J. Environ. Res. Public Health 15, no. 8: 1784.
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