Effects of topiramate on sustained repetitive firing and spontaneous recurrent seizure discharges in cultured hippocampal neurons.
In this study, we examined the effects of topiramate (TPM) on the electrophysiologic properties of cultured rat hippocampal pyramidal neurons.



Whole-cell current-clamp recording techniques were used to determine the effects of TPM on sustained repetitive firing (SRF), spontaneous epileptiform-burst firing, and spontaneous recurrent seizures (SRS).



Topiramate at therapeutic concentrations (10-100 microM) significantly decreased or abolished SRF in a dose-dependent and partially reversible manner. When transiently exposed to a medium in which Mg2+ is omitted, hippocampal neurons in culture develop SRS ("epilepsy") and epileptiform discharges. Application of TPM at concentrations ranging from 10 to 100 microM to cells displaying seizure activity caused a concentration-dependent decrease in the number of action potentials within a burst and in the average duration of epileptiform activity. Both effects were partially reversed during a 5- to 30-min drug washout period.



These effects on the electrophysiologic properties of cultured neurons are consistent with the concept that TPM exerts modulatory effects on voltage-dependent Na+ and/or Ca2+ conductances responsible for the generation and propagation of action potentials. Topiramate also may inhibit synaptic conductances responsible for transmission of epileptiform discharges.
DeLorenzo
R J
RJ
Department of Neurology, Medical College of Virginia, Richmond, USA.
Sombati
S
S
Coulter
D A
DA
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000503:physiopathology / Q000517:prevention & control*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D010672:Phenytoin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D000077236:Topiramate
D000927:Anticonvulsants; D015220:Calcium Channels; D015222:Sodium Channels; D000077236:Topiramate; D005632:Fructose; D010672:Phenytoin