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.
Armand
V
V
Department of Neurophysiology, Humboldt University Berlin, Germany.
Rundfeldt
C
C
Heinemann
U
U
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000187:drug effects*; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
C108937:AWD 140-190; D000927:Anticonvulsants; D009025:Morpholines; D011392:Proline; D008274:Magnesium; D011188:Potassium; D002118:Calcium