The effects of perampanel, lacosamide, and lamotrigine on secondary generalized (SG) seizures in a rat amygdala kindling model (P2.234)

Objective: To explore the role of AMPA receptors in SG seizures through the application of perampanel in a rat amygdala kindling model, with a comparison of the effects of sodium channel blockade by lacosamide and lamotrigine. Background: Perampanel is a non-competitive AMPA receptor antagonist approved for adjunctive treatment of partial-onset seizures, with or without SG seizures, and primary generalized tonic-clonic seizures. In Phase III trials in patients with partial-onset seizures, adjunctive perampanel conferred greater seizure control than placebo in patients with secondary generalization (Steinhoff et al. Epilepsia 2013; 54: 1481–1489). Design/Methods: On the first day, male Wistar-Kyoto rats (n=20) received increasing electrical stimulation in the basolateral amygdala until the after-discharge threshold (ADT) was reached. They then received daily stimulation at the ADT until three Racine score 5 seizures occurred consecutively. Perampanel (0.25–1.5 mg/kg), lacosamide (7.5–30 mg/kg), lamotrigine (5–20 mg/kg), or vehicle was administered intraperitoneally. Drug effects on Racine score (seizure severity) and Score 4 latency (S4L; an index of generalization rate) at the ADT stimulation were measured. Seizure severity was analyzed by Dunn’s multiple comparison tests, and S4L by Dunnett’s multiple comparison tests. Results: Perampanel conferred dose-dependent reductions in seizure severity and increases in S4L. Compared with vehicle, average Racine score was significantly reduced to 1.8 by perampanel 1.5 mg/kg ( P P P P P P Conclusions: In a rat amygdala kindling model, perampanel increased latency to SG seizures at doses that were suboptimal for reducing seizure severity, suggesting that AMPA receptors play an important role in secondary generalization. Study Supported by: Eisai Co., Ltd. Disclosure: Dr. Ting has received personal compensation for activities with Eisai as an employee. Dr. Kaneko has nothing to disclose. Dr. Ido has received personal compensation for activities with Eisai as an employee.