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

Year: 2008

Type: article

Abstract: 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.

Source: Epilepsia

DOI: 10.1111/j.1528-1167.2008.01759.x

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

Institutions: The Royal Melbourne Hospital, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, UNSW Sydney

Language: English

Topic: Epilepsy research and treatment

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Novartis Pharma, Medical Research Council, National Health and Medical Research Council