Effects of new valproate derivatives on epileptiform discharges induced by pentylenetetrazole or low Mg²⁺ in rat entorhinal cortex-hippocampus slices

Abstract 

The effects of four valproic acid derivatives were studied on pentylenetetrazole-induced epileptiform discharges in combined entorhinal cortex hippocampus slices. The two new sugar-esters of valproic acid, dimethylenexylitol valproate (VDMX, 0.5 mM) and glucose valproate (VG, 2 mM) abolished the epileptiform activity. These two new derivatives were compared to two clinically used anticonvulsant drugs, valpromide (2 mM) which suppressed the activity and valproic acid (2 mM), which was ineffective. The new drugs VDMX and VG were also tested on different patterns of epileptiform activity induced by lowering of [Mg²⁺]₀. A 1 mM concentration of VDMX and 2 mM VG, reversibly suppressed the recurrent short discharges in area CA1 and the seizure-like events in the entorhinal cortex. A concentration of 2 mM VDMX was required to abolish the late recurrent discharges in entorhinal cortex. VG at 2 mM reduced the frequency of these discharges by 58.5±9.5%.

Keywords:  Dimethylenexylitol valproate, Sugar-ester, Valpromide, Valproic acid, Seizure-like event, Late recurrent discharges