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 Mg(2+)-free ACSF and N-methyl-D-aspartate (NMDA)-containing ACSF induced epileptiform afterdischarges following evoked responses. Pretreatment of slices by bath application of 100 microM Mem for 18-20 min prevented epileptiform afterdischarges under both convulsant conditions. Perfusion with 100 microM Mem alone for up to 50 min had no discernible effect on evoked responses. MK-801 was as effective at < or = 10 microM 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 MG(2+)-free ACSF. The EC50 of Mem was 16.6 microM and that of MK-801 was 0.19 microM 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.
Apland
J P
JP
Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Cann
F J
FJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000927:Anticonvulsants; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D008559:Memantine