Comparison of effects of valproate and trans-2-en-valproate on different forms of epileptiform activity in rat hippocampal and temporal cortex slices.
OBJECTIVE
Reducing the extracellular magnesium or calcium or increasing the extracellular potassium induces different patterns of epileptiform activity in the hippocampus and the entorhinal cortex. Although in the low Ca2+ and K+ models, seizure-like events (SLEs) develop in area CA1 of the hippocampus, only short recurrent discharges develop in the low Mg2+ model. In contrast, in low Mg2+, SLEs and late recurrent discharges (LRDs) are observed in the entorhinal cortex.


METHODS
We compared the effects of valproate (VPA) and its major metabolite, trans-2-en-VPA (TVPA), on all these different model activities using extracellular field potential measurements. We also investigated the equilibration time course of VPA in the slice by using VPA-sensitive microelectrodes.


RESULTS
Both drugs reversibly blocked most forms of epileptiform activity. The only exception was the LRDs in the entorhinal cortex. In paired experiments, TVPA appeared to be more effective than VPA bath applied with the same concentration to the same slice. With our measurements of the VPA concentrations in slices, we showed that the concentrations used were close to therapeutic drug levels.


CONCLUSIONS
If TVPA stands the toxicological tests, it might be a useful alternative in the treatment of seizures.
Sokolova
S
S
Institut für Physiologie der Charité, Abteilung Neurophysiologie, Humboldt Universität Berlin, Germany.
Schmitz
D
D
Zhang
C L
CL
Löscher
W
W
Heinemann
U
U
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004569:Electroencephalography; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology; D004827:Epilepsy / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D008274:Magnesium / Q000378:metabolism; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013702:Temporal Lobe / Q000187:drug effects* / Q000503:physiopathology*; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D005229:Fatty Acids, Monounsaturated; C014168:2-propyl-2-pentenoic acid; D014635:Valproic Acid; D008274:Magnesium