Differential effect of carbamazepine and oxcarbazepine on excitatory synaptic transmission in rat hippocampus

Michela Giustizieri, Marta Armogida, Nicola Berretta, Mauro Federici, Silvia Piccirilli, Nicola B. Mercuri, Robert Nistico

Research output: Contribution to journalArticle

Abstract

In this study, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), both in current use for the treatment of epilepsy and bipolar disorder, on fast excitatory transmission in rat hippocampal slices. Using electrophysiological recordings, we have investigated the effects of CBZ and OXC on repetitive action potential discharge of CA1 pyramidal neurons demonstrating that both compounds produced firing inhibition with similar IC50 values. Moreover, we show that bath applied CBZ (0.01-1 mM) exerted a concentration-dependent decrease in the amplitude of the field excitatory postsynaptic potentials with an IC 50 of ∼194.3 μM. When OXC was used at the same concentrations, the concentration-response curve was shifted to the right (IC50 of ∼711.07 μM). In addition, we demonstrated that CBZ and OXC reduced, to a different extent, both evoked excitatory postsynaptic currents and NMDA-, AMPA-, and KA-mediated inward currents, CBZ being more potent than OXC. These data highlight distinct presynaptic and postsynaptic sites of action for both compounds and suggest that CBZ, by markedly depressing postsynaptic ionotropic glutamate receptors-mediated responses, may produce more severe cognitive and memory impairment. Thus, we assume that relatively high doses of OXC could be better tolerated than therapeutically equivalent doses of CBZ, justifying the preferential use of OXC as first-line treatment in the therapy of neurological and psychiatric disorders, particularly when compared with CBZ.

Original languageEnglish
Pages (from-to)783-789
Number of pages7
JournalSynapse
Volume62
Issue number10
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Antiepileptic drugs
  • Glutamate receptors
  • Hippocampus
  • Patch clamp recordings
  • Sodium channels

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)
  • Advanced and Specialised Nursing
  • Pharmacology

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