Journal article
Oxcarbazepine, not its active metabolite, potentiates GABAA activation and aggravates absence seizures
T Zheng, AL Clarke, MJ Morris, CA Reid, S Petrou, TJ O'Brien
Epilepsia | WILEY | Published : 2009
Abstract
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, s..
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Awarded by Australian National Health and Medical Research Council
Funding Acknowledgements
[ "The authors are grateful to Novartis Pharma AG, Basel, Switzerland, for the gift of the MHD, and to Dr. Markus Schmutz Ph.D., B.Sc., Novartis Distinguished Scientist, for his helpful comments on the manuscript. We also thank Chantel Trager and Dragica Maric for their technical help with the oocyte recordings. The study was supported by a Project grant from the Australian National Health and Medical Research Council to M.J.M., T.J.O., and C.A.R. (NH&MRC Project grant no. 400106), Novartis Pharma by the gift of drug (MHD), and an equipment loan from Compumedics, Melbourne, Australia.", "Conflict of interest: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. T.J.O. has received support from Novartis Pharma Australia. None of the other authors have any conflicts of interest to disclose." ]