Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist

Rafal M. Kaminski, Madhumita Banerjee, Michael A Rogawski

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Although the mechanism of action of topiramate is not fully understood, its anticonvulsant properties may result, at least in part, from an interaction with AMPA/kainate receptors. We have recently shown that topiramate selectively inhibits postsynaptic responses mediated by GluR5 kainate receptors. To determine if this action of topiramate is relevant to the anticonvulsant effects of the drug in vivo, we determined the protective activity of topiramate against seizures induced by intravenous infusion of various ionotropic glutamate receptor agonists in mice. Topiramate (25-100 mg/kg, i.p.) produced a dose-dependent elevation in the threshold for clonic seizures induced by infusion of ATPA, a selective agonist of GluR5 kainate receptors. Topiramate was less effective in protecting against clonic seizures induced by kainate, a mixed agonist of AMPA and kainate receptors. Topiramate did not affect clonic seizures induced by AMPA or NMDA. In contrast, the thresholds for tonic seizures induced by higher doses of these various glutamate receptor agonists were all elevated by topiramate. Unlike topiramate, carbamazepine elevated the threshold for AMPA- but not ATPA-induced clonic seizures. Our results are consistent with the possibility that the effects of topiramate on clonic seizure activity are due to functional blockade of GluR5 kainate receptors. Protection from tonic seizures may be mediated by other actions of the drug. Together with our in vitro cellular electrophysiological results, the present observations strongly support a unique mechanism of action of topiramate, which involves GluR5 kainate receptors.

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalNeuropharmacology
Volume46
Issue number8
DOIs
StatePublished - Jun 2004
Externally publishedYes

Keywords

  • AMPA
  • Carbamazepine
  • GluR5
  • Kainate
  • Mouse
  • NMDA
  • Seizure
  • Topiramate

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Fingerprint Dive into the research topics of 'Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist'. Together they form a unique fingerprint.

  • Cite this