EFFECTS OF AWD-140-190 ON STIMULUS-INDUCED FIELD POTENTIALS AND ON DIFFERENT PATTERNS OF EPILEPTIFORM ACTIVITY-INDUCED BY LOW-CALCIUM OR LOW MAGNESIUM IN RAT ENTORHINAL CORTEX HIPPOCAMPAL SLICES

AWD 140-190 a potent new anticonvulsant was tested on several types of epileptiform activities in entorhinal cortex hippocampal slices. AWD 140-190 suppressed completely and in a dose-dependent manner spontaneo us seizure-like events induced by lowering extracellular Ca2+. In the low magnesium model, AWD 140-190 applied with 200 mu M reduced recurre nt short discharges in area CA1 by 48.1 +/- 14.7%, while in the entorh inal cortex seizure-like events were not depressed. Late recurrent dis charges were increased in frequency to 213.8 +/- 78.1 and reduced in a mplitude by 50.1 +/- 14.4%. Responses to paired pulse stimuli with int ervals ranging from 20 to 150 ms were reduced both with alvear and str atum radiatum stimulation. Decreases in [Ca2+](0) and associated slow field potentials evoked by repetitive stimulation of stratum radiatum were also depressed in a dose-dependent manner. AWD 140-190 also reduc ed stimulus-induced rises in [K+](0). AWD 140-190 200 mu M diminished the amplitude of slow field potentials observed during high K+-induced spreading depression by about 17% in CA1 and 34% in entorhinal cortex without any significant effect on SD-associated rises in [K+](0). The se results suggest that AWD 140-190 has an anticonvulsant effect presu mably by interfering with repetitive generation of action potentials. AWD 140-190 may also possess modulatory, effects on glial cells as sug gested by the strong depression of SD-associated slow negative potenti al shifts. (C) 1997 Elsevier Science B.V.