ANTICONVULSANT EFFECTS OF MEMANTINE AND MK-801 IN GUINEA-PIG HIPPOCAMPAL SLICES

The anticonvulsant properties of memantine (Mem) were compared to those of MK-801. Extracellular field recordings were obtained from area CA1 of guinea pig hippocampal slices in a total submersion chamber at 32 degrees C in normal oxygenated artificial cerebrospinal fluid (ACSF). Evoked responses were elicited by 0.07 Hz stimulation of the Schaffer collateral and commissural fibers. Bath perfusion of slices with Mg2+-free ACSF and N-methyl-D-aspartate (NMDA)-containing ACSF induced epileptiform afterdischarges following evoked responses. Pretreatment of slices by bath application of 100 mu M Mem for 18-20 min prevented epileptiform afterdischarges under both convulsant conditions. Perfusion with 100 mu M Mem alone for up to 50 min had no discernible effect on evoked responses. MK-801 was as effective at less than or equal to 10 mu M and required application for over 15 min to suppress afterdischarges completely. Both Mem and MK-801 suppressed epileptiform activity when applied after such activity was induced by NMDA or Mg2+-free ACSF. The EC50 of Mem was 16.6 mu M and that of MK-801 was 0.19 mu M for blocking NMDA-induced evoked response suppression. Thus, in the guinea pig hippocampal slice preparation, Mem appeared to have anticonvulsant properties qualitatively similar to those of MK-801, but was 10-100 fold less potent.