title: Oxcarbazepine and its active metabolite, (S)-licarbazepine, exacerbate seizures in a mouse model of genetic generalized epilepsy.
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/kg) all significantly increased the number of SWDs, while their duration was unaffected. The potential for (S)-licarbazepine to exacerbate SWDs suggests that eslicarbazepine acetate should be used with caution in generalized epilepsy. Furthermore, generalized seizure exacerbation for first-, second-, and third-generation carbamazepine-based compounds is likely to occur through a common mechanism.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Melbourne, Australia.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reid
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D058256:Brain Waves / Q000187:drug effects*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004829:Epilepsy, Generalized / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D000078330:Oxcarbazepine; D011963:Receptors, GABA-A / Q000235:genetics*; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; D011963:Receptors, GABA-A; D002220:Carbamazepine; D014635:Valproic Acid; C571001:eslicarbazepine; D000078330:Oxcarbazepine
keywords: Antiepileptic drugs; Epilepsy; Seizure aggravation; Spike-and-wave