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

Abstract

Summary 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..