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

Int J Environ Res Public Health. 2018 Aug 20;15(8):1784. doi: 10.3390/ijerph15081784.


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: GABA; anticonvulsant; brain; calcium channel; drug discovery; electrophysiology; enaminones; epilepsy; neuron; sodium channel.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / therapeutic use*
  • Benzamides / chemical synthesis*
  • Benzamides / therapeutic use*
  • Cell Line
  • Neurons / drug effects
  • Patch-Clamp Techniques
  • Rodentia


  • Anticonvulsants
  • Benzamides