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Journal Article

Effects of the tetronic acid derivatives AO33 (losigamone) and AO78 on epileptiform activity and on stimulus−induced calcium concentration changes in rat hippocampal slices

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Köhr,  Georg
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;
Directly responsible to the Managing Director, Max Planck Institute for Medical Research, Max Planck Society;
Georg Köhr Group, Max Planck Institute for Medical Research, Max Planck Society;

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Citation

Köhr, G., & Heinemann, U. (1990). Effects of the tetronic acid derivatives AO33 (losigamone) and AO78 on epileptiform activity and on stimulus−induced calcium concentration changes in rat hippocampal slices. Epilepsy Res., 7(1), 49-58. doi:10.1016/0920-1211(90)90053-X.


Abstract
The effects of members of a new class anticonvulsants, the tetronic acid derivatives, were studied in 3 in vitro models of epileptogenesis in rat hippocampal slices; the picrotoxin, the low magnesium and the low calcium model. The effects of AO33 (losigamone) and AO78 on stimulus−induced decreases in extracellular calcium concentration were also investigated. In all 3 models of epileptogenesis, both drugs blocked spontaneous and reduced stimulus−induced epileptiform discharges dose dependently and reversibly. Stimulus−induced changes in [Ca2+]0 were markedly diminished by these agents. The fact that the tetronic acid derivatives block the low Ca seizure−like events which develop independently from chemical synaptic transmission suggests that these agents have non−synaptic or direct membrane actions with subsequently reduced cellular excitability