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  • Title: Pre- and post-exposure talampanel (GYKI 53773) against kainic acid seizures in neonatal rats.
    Author: Dhir A, Chavda V.
    Journal: Pharmacol Rep; 2016 Feb; 68(1):190-5. PubMed ID: 26721372.
    Abstract:
    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 4mg/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 4mg/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 (2.5-10mg/kg, ip) 30min before kainic acid did not affect the onset of kainic acid convulsions. Talampanel at 20mg/kg, ip delayed the commencement of tonic extension, but not status-induced by kainic acid. In contrast, talampanel (5 and 10mg/kg, ip) when administered 5min after kainic acid (4mg/kg, ip) postponed the onset of status epilepticus and tonic extension compared to vehicle treated group. Furthermore, talampanel (10mg/kg, ip) but not GYKI 52466 (20 or 50mg/kg, ip; a non-competitive AMPA/kainate receptor antagonist) stopped the ongoing status epilepticus when administered 10min after the administration of kainic acid. However, seizures re-occurred after 35.98±2.36min. 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.
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