title: Pre- and post-exposure talampanel (GYKI 53773) against kainic acid seizures in neonatal rats.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuropharmacology Division, Institute of R&D, Gujarat Forensic Sciences University, Gandhinagar, India. Electronic address: ashishdhirpu@yahoo.com.
authors.forename: Ashish
authors.initials: A
authors.lastname: Dhir
authors.affiliation: Neuropharmacology Division, Institute of R&D, Gujarat Forensic Sciences University, Gandhinagar, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Chavda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D001569:Benzodiazepines; C085266:talampanel; D007608:Kainic Acid
keywords: Kainic acid; Neonatal seizures; Post-exposure; Pre-exposure; Talampanel