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Updated: Jul 2, 2026

Generation of Local CA1 γ Oscillations by Tetanic Stimulation
Published on: August 14, 2015
Oxcarbazepine, not its active metabolite, potentiates GABAA activation and aggravates absence seizures
Thomas Zheng1, Alison L Clarke, Margaret J Morris
1Department of Medicine The University of Melbourne, The Royal Melbourne Hospital, Victoria, Australia.
Purpose:
Studies in genetic absence epileptic rats from Strasbourg (GAERS) indicate that enhancement of gamma aminobutyric acid (GABA(A)) 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 GABA(A) receptor current and aggravate seizures.
Methods:
In vitro studies in Xenopus oocytes compared the three drugs' effect on GABA(A) receptor currents. In vivo studies compared seizure activity in GAERS after intraperitoneal drug administration.
Results:
OXC potentiated GABA(A) receptor current and aggravated seizures in GAERS, similarly to the effect of CBZ. Conversely, MHD showed only a minor potentiation of GABA(A) receptor current and did not aggravate seizures.
Discussion:
A hydroxyl group at the C-10 position on the CBZ tricyclic structure in MHD reduces GABA(A) 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.
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