Oxcarbazepine, not its active metabolite, potentiates GABAA activation and aggravates absence seizures

Thomas Zheng, Alison L. Clarke, Margaret J. Morris, Christopher A. Reid, Steven Petrou, Terence J. O'Brien

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)


Purpose: Studies in genetic absence epileptic rats from Strasbourg (GAERS) indicate that enhancement of γ aminobutyric acid (GABAA) receptor activity is a critical mechanism in the aggravation of seizures by carbamazepine (CBZ). We examined whether structural analogs of CBZ, oxcarbazepine (OXC), and its active metabolite, monohydroxy derivative (MHD), also potentiate GABAA receptor current and aggravate seizures. Methods: In vitro studies in Xenopus oocytes compared the three drugs' effect on GABAA receptor currents. In vivo studies compared seizure activity in GAERS after intraperitoneal drug administration. Results: OXC potentiated GABAA receptor current and aggravated seizures in GAERS, similarly to the effect of CBZ. Conversely, MHD showed only a minor potentiation of GABAA receptor current and did not aggravate seizures. Discussion: A hydroxyl group at the C-10 position on the CBZ tricyclic structure in MHD reduces GABAA receptor potentiation and seizure aggravation. Reports of the aggravation of absence seizures in patients taking OXC may result from circulating unmetabolized OXC rather than MHD.

Original languageEnglish
Pages (from-to)83-87
Number of pages5
Issue number1
Publication statusPublished - Jan 2009
Externally publishedYes


  • Absence seizures
  • Carbamazepine
  • Oxcarbazepine
  • Seizure aggravation

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