Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats

• DOI: 10.14581/jer.15010
• Publication Date: 2016-01-14T12:31:59Z
• Authors: LK Friedman; AM Slomko; JP Wongvravit; Z Naseer; S Hu; WY Wan; SS Ali
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Original Article; 3. Good health

The efficacy of retigabine (RGB), a positive allosteric modulator K+ channels indicated for adjunct treatment partial seizures, was studied in two adult models kainic acid (KA)-induced status epilepticus to determine it's toleratbility.Retigabine administered systemiclly at high (5 mg/kg) and low (1-2 doses either 30 min prior or 2 hr after KA-induced epilepticus. High (1 µg/µL) (0.25 concentrations RGB were also delivered by intrahippocampal microinjection the presence KA.Dose-dependent effects observed with both models. Lower increased seizure behavior latency reduced number single spikes synchronized burst events electroencephalogram (EEG). Higher worsened behavior, produced severe ataxia, spiking activity. Animals treated that resistant seizures did not exhibit significant injury loss GluR1 expression; however if stage 5-6 reached, typical hippocampal depletion subunit protein vulernable pyramidal fields occurred.RGB neuroprotective only significantly attenuated. simultaneously suppressed granule cell layer which may weaken excitatory transmission. Biphasic herein suggest human dosage must be carefully scrutinized produce optimal clinical response.