Add time:08/02/2019         Source:sciencedirect.com

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.

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