title: Effects of topiramate on sustained repetitive firing and spontaneous recurrent seizure discharges in cultured hippocampal neurons.
abstract: 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.
authors.affiliation: Department of Neurology, Medical College of Virginia, Richmond, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: DeLorenzo
authors.forename: S
authors.initials: S
authors.lastname: Sombati
authors.forename: D A
authors.initials: DA
authors.lastname: Coulter
mesh_terms: 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
chemical_list: D000927:Anticonvulsants; D015220:Calcium Channels; D015222:Sodium Channels; D000077236:Topiramate; D005632:Fructose; D010672:Phenytoin