NYMC Faculty Publications

Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats

Author Type(s)

Faculty

DOI

10.14581/jer.15010

Journal Title

Journal of Epilepsy Research

First Page

46

Last Page

59

Document Type

Article

Publication Date

12-1-2015

Department

Cell Biology and Anatomy

Second Department

Physical Therapy

Disciplines

Medicine and Health Sciences

Abstract

BACKGROUND AND PURPOSE: 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.

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