Age dependent effects of Retigabine on absence seizure in WAG/Rij rats; an experimental study

Retigabine (RTG, Ezogabine, DC23129) is the first neuronal potassium channel opener in the treatment of epilepsy and exerts its effects through the activation of neuronal KCNQ2/3 potassium channels; in higher doses, it acts also on sodium and voltage‐gated calcium channels. The aim of this study was to investigate possible age‐dependent therapeutic effects of RTG on spike‐and‐wave discharges (SWD) in an animal model of absence epilepsy using WAG/Rij rats. In this study, 6‐ and 12‐month‐old WAG/Rij rats were used. For both age categories, three sub‐groups that consisted of one control group (n=7) by the administration of 20% DMSO (control) and two study groups by the administration of 5 mg/kg (n=7) and 15 mg/kg RTG (n=7) were designed. EEG electrodes were placed onto the skull of anaesthetized animals; and baseline EEG was recorded for one hour after a recovery period from surgery. Then, the pre‐determined two distinct doses of RTG and 20% DMSO were administered as a solvent via intraperitoneal injections, and EEG was recorded for 3 hours. After injection, both doses of RTG increased the total SWD number and duration of SWD in the first and second hours in 12‐month‐old rats. These parameters were elevated compared to 6‐month‐old rats. Age‐dependent effects of RTG were observed in SWD activity. Pro‐epileptic effects in middle‐aged WAG/Rij rats were demonstrated in both RTG doses. Differences in the distribution of KCNQ2/3 channels and switch of GABAergic system from inhibitory to excitatory with age might contribute to increased SWD activity in middle‐aged rats.