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

Abstract	The effects of members of a new class of 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.
Authors	G Köhr, U Heinemann
Journal	Epilepsy research (Epilepsy Res) Vol. 7 Issue 1 Pg. 49-58 ( 1990) ISSN: 0920-1211 [Print] Netherlands
PMID	2292246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Furans Picrotoxin A 078 losigame Magnesium Calcium
Topics	Animals Calcium (metabolism) Electric Stimulation Epilepsy (chemically induced, metabolism, physiopathology) Extracellular Space (metabolism) Furans (pharmacology) Hippocampus (metabolism) In Vitro Techniques Magnesium (metabolism) Osmolar Concentration Picrotoxin Rats Synapses (metabolism)

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