Pre- and post-exposure talampanel (GYKI 53773) against kainic acid seizures in neonatal rats

Background: AMPA receptors play an important role in the neurobiology of neonatal epilepsy. The present study evaluated the effect of talampanel, a potent and selective non-competitive antagonist of AMPA receptors, against kainic acid-induced continuous seizures (status epilepticus) and other behavioral abnormalities in neonatal rats. Methods: Kainic acid was administered at doses of 2 or 4 mg/kg, ip to induce seizures and status epilepticus in postnatal 7 days old rat neonates in pre- and post-exposure studies, respectively. Results: Intraperitoneal administration of kainic acid (2 or 4 mg/kg) resulted in forelimb/hind-limb scratching defined as automatism, continuous generalized tonic-clonic seizures with loss of righting reflex suggesting status epilepticus and tonic extension. Pre-exposure of talampanel (2.5-10 mg/kg, ip) 30 min before kainic acid did not affect the onset of kainic acid convulsions. Talampanel at 20 mg/kg, ip delayed the commencement of tonic extension, but not status-induced by kainic acid. In contrast, talampanel (5 and 10 mg/kg, ip) when administered 5 min after kainic acid (4 mg/kg, ip) postponed the onset of status epilepticus and tonic extension compared to vehicle treated group. Furthermore, talampanel (10 mg/kg, ip) but not GYKI 52466 (20 or 50 mg/kg, ip; a non-competitive AMPA/kainate receptor antagonist) stopped the ongoing status epilepticus when administered 10 min after the administration of kainic acid. However, seizures re-occurred after 35.98 +/- 2.36 min. Conclusion: The present results suggested that talampanel is protective in kainic acid-induced neonatal status epilepticus model; however, the time of administration is a crucial factor in determining its effectiveness. (c) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.