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 spontaneous seizure-like events induced by lowering extracellular Ca2+. In the low magnesium model, AWD 140-190 applied with 200 microM reduced recurrent short discharges in area CA1 by 48.1 +/- 14.7%, while in the entorhinal cortex seizure-like events were not depressed. Late recurrent discharges were increased in frequency to 213.8 +/- 78.1 and reduced in amplitude by 50.1 +/- 14.4%. Responses to paired pulse stimuli with intervals ranging from 20 to 150 ms were reduced both with alvear and stratum 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 reduced stimulus-induced rises in [K+]0. AWD 140-190 200 microM 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. These results suggest that AWD 140-190 has an anticonvulsant effect presumably by interfering with repetitive generation of action potentials. AWD 140-190 may also possess modulatory effects on glial cells as suggested by the strong depression of SD-associated slow negative potential shifts.