Molecular Docking Studies on Anticonvulsant Enaminones Inhibiting Voltage-Gated Sodium Channels

Epilepsy is described as the most common chronic brain disorder. A typical symptom of epilepsy results in uncontrolled convulsions caused by temporary excessive neuronal discharges. Although, several new anticonvulsants have been introduced, some types of seizures have still not been adequately controlled with these new and current therapies. There is an urgent need to develop new anticonvulsant drugs to control the many different types of seizures. Many studies have shown that the epilepsies involve more than one mechanism and therefore may be responsible for the various types of observed seizures. Recently reported studies have shown that a group of newly synthesized 6 Hz active anticonvulsant fluorinated N-benzamide enaminones to exhibited selective inhibitions of voltage-gated sodium (Na_v) channels. Na_v channels are responsible for the initial inward currents during the depolarization phases of the action potential in excitable cells. The activation and opening of Na_v channels result in the initial phases of action potentials. We hypothesize that there is an essential pharmacophore model for the interactions between these enaminones and the active sites of Na_v channels. The research reported here is focused on molecular docking studies of the interactions that occur between the fluorinated N-benzamide enaminones and the Na_v channels. These studies may open an avenue for designing anticonvulsant drugs by inhibiting Na_v channels.