EFFECTS OF NEW VALPROATE DERIVATIVES ON EPILEPTIFORM DISCHARGES INDUCED BY PENTYLENETETRAZOLE OR LOW MG2-HIPPOCAMPUS SLICES( IN RAT ENTORHINAL CORTEX)

The effects of four valproic acid derivatives were studied on pentylen etetrazole-induced epileptiform discharges in combined entorhinal cort ex hippocampus slices. The two new sugar-esters of valproic acid, dime thylenexylitol valproate (VDMX, 0.5 mM) and glucose valproate (VG, 2 m M) abolished the epileptiform activity. These two new derivatives were compared to two clinically used anticonvulsant drugs, valpromide (2 m M) which suppressed the activity and valproic acid (2 mM), which was i neffective. The new drugs VDMX and VG were also tested on different pa tterns of epileptiform activity induced by lowering of [Mg2+](0). A 1 mM concentration of VDMX and 2 mM VG, reversibly suppressed the recurr ent short discharges in area CA1 and the seizure-like events in the en torhinal 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%. (C) 1998 Elsevier Science B.V. All rights reserved.