Oxcarbazepine and its active metabolite, (S)-licarbazepine, exacerbate seizures in a mouse model of genetic generalized epilepsy

Tae Hwan Kim; Christopher A Reid; Steven Petrou

Journal article

Oxcarbazepine and its active metabolite, (S)-licarbazepine, exacerbate seizures in a mouse model of genetic generalized epilepsy

Tae Hwan Kim, Christopher A Reid, Steven Petrou

EPILEPSIA | WILEY | Published : 2015

DOI: 10.1111/epi.12866

Abstract

Oxcarbazepine (OXC), widely used to treat focal epilepsy, is reported to exacerbate seizures in patients with generalized epilepsy. OXC is metabolized to monohydroxy derivatives in two enantiomeric forms: (R)-licarbazepine and (S)-licarbazepine. Eslicarbazepine acetate is a recently approved antiepileptic drug that is rapidly metabolized to (S)-licarbazepine. It is not known whether (S)-licarbazepine exacerbates seizures. Here, we test whether OXC or either of its enantiomers exacerbates the number of spike-and-wave discharges (SWDs) in mice harboring the human γ-aminobutyric acid A receptor (GABAA)γ2(R43Q) mutation. OXC (20 mg/kg), (S)-licarbazepine (20 mg/kg), and (R)-licarbazepine (20 mg/..

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University of Melbourne Researchers

Steven Petrou Author Florey Department of Neuroscience and Mental Health

Christopher Reid Author Medicine - Austin Health

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Grants

Awarded by National Health and Medical Research Council (NHMRC) program grant

Awarded by NMHRC fellowship

Funding Acknowledgements

Supported by National Health and Medical Research Council (NHMRC) program grant 400121 to SP. SP acknowledges support from a NMHRC fellowship (1005050). CAR also acknowledges the support of the Dowd Fellowship. The Angior Foundation supported the purchase of equipment. The Florey Institute of Neuroscience and Mental Health is supported by Victorian State Government infrastructure funds.