Electrophysiological actions of felbamate on rat striatal neurones

A. Pisani, A. Stefani, A. Siniscalchi, N. B. Mercuri, G. Bernardi, P. Calabresi

Research output: Contribution to journalArticle

Abstract

1. We have investigated the effects of the anticonvulsant drug, felbamate (FBM), on striatal neurones, recorded in vitro by using both intracellular and extracellular conventional recordings in slices and whole-cell recordings in acutely isolated neurones. 2. FBM, at therapeutically relevant concentrations (30-300 μM) showed multiple mechanisms of action. Like other antiepileptic drugs, FBM (30-300 μM) showed a direct inhibitory action on current-evoked firing discharge of striatal neurones. A patch-clamp analysis of this effect revealed a dose-related reduction of voltage-dependent sodium (Na+) currents (10-100 μM), with a half inhibition dose (IC50) value of 28 μM. 3. We also tested whether FBM affected corticostriatal glutamatergic transmission. In control medium (1.2 mM external magnesium), both extracellularly recorded field potentials and intracellularly recorded excitatory postsynaptic potentials (e.p.s.ps) evoked by cortical stimulation were not affected by bath application of 30-300 μM FBM. 4. When magnesium was removed from the perfusing solution, a procedure which reveals a N-methyl-D-aspartate (NMDA)-mediated component in the corticostriatal synaptic potential, FBM (30-300 μM) produced a dose-dependent reduction of the amplitude of both the field potential and the e.p.s.p. 5. FBM reduced the inward currents produced either by bath or by focal applications of 30 μM NMDA, a finding consistent with the hypothesis that the observed reduction of the NMDA-mediated component of the synaptic potentials may be caused at postsynaptic level. 6. The reduction of the NMDA-mediated component of the synaptic transmission by FBM and its depressant effect on the voltage-dependent Na+ channels, may account for the antiepileptic action of this drug. Moreover, the pharmacological properties of FBM might render this drug interesting as a neuroprotectant agent.

Original languageEnglish
Pages (from-to)2053-2061
Number of pages9
JournalBritish Journal of Pharmacology
Volume116
Issue number3
Publication statusPublished - 1995

Keywords

  • Antiepileptic drugs
  • Excitatory amino acids
  • Felbamate
  • NMDA
  • Patch-clamp
  • Sodium channels
  • Striatum
  • Synaptic potentials

ASJC Scopus subject areas

  • Pharmacology

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