title: Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats.
abstract: OBJECTIVE
  The efficacy of retigabine (RGB), a positive allosteric modulator of K+ channels indicated for adjunct treatment of partial seizures, was studied in two adult models of kainic acid (KA)-induced status epilepticus to determine it's toleratbility.
  
  
  METHODS
  Retigabine was administered systemiclly at high (5 mg/kg) and low (1-2 mg/kg) doses either 30 min prior to or 2 hr after KA-induced status epilepticus. High (1 µg/µL) and low (0.25 µg/µL) concentrations of RGB were also delivered by intrahippocampal microinjection in the presence of KA.
  
  
  RESULTS
  Dose-dependent effects of RGB were observed with both models. Lower doses increased seizure behavior latency and reduced the number of single spikes and synchronized burst events in the electroencephalogram (EEG). Higher doses worsened seizure behavior, produced severe ataxia, and increased spiking activity. Animals treated with RGB that were resistant to seizures did not exhibit significant injury or loss in GluR1 expression; however if stage 5-6 seizures were reached, typical hippocampal injury and depletion of GluR1 subunit protein in vulernable pyramidal fields occurred.
  
  
  CONCLUSIONS
  RGB was neuroprotective only if seizures were significantly attenuated. GluR1 was simultaneously suppressed in the resistant granule cell layer in presence of RGB which may weaken excitatory transmission. Biphasic effects observed herein suggest that the human dosage must be carefully scrutinized to produce the optimal clinical response.
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Friedman
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Slomko
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Wongvravit
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Naseer
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: W Y
authors.initials: WY
authors.lastname: Wan
authors.affiliation: Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Ali
keywords: AMPA receptor; Anticonvulsant; Epilepsy; Hippocampus; Neurodegeneration; Retigabine
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