Effect of sodium valproate and flunarizine administered alone and in combination on pentylenetetrazole model of absence seizures in rat.

Sodium valproate (VPA) and flunarizine (FLU) administered individually and together were examined for their effects on behavioural, and EEG changes in the pentylenetetrazole (PTZ) induced rat model of absence seizures. PTZ, 20 mg/kg, i.p., produced behavioural staring and immobility with concomitant, repetitive 7 to 9 Hz spike/wave discharges (SWDs) in EEG, monitored continuously for 1 hr and thereafter, intermittently for 4 hr, post-vehicle/drug. The number and duration (sec) of SWDs/hr were the parameters used for evaluation of vehicle vs. drug effects in normal as well as rats made epileptogenic by repeated cortical stimulation. VPA, 200 mg/kg, i.p., produced a significant reduction in the number and duration of SWDs at 20 min only in epileptogenic rats, declining to non-significant levels at 60 min, whereas FLU, 10 mg/kg i.p. had no effect on either parameter. The combination of VPA and FLU produced a highly significant reduction of the number and duration of SWDs/h for 60 min in normal and epileptogenic rats. The results provide evidence for a synergistic effect of VPA and FLU in experimental absence seizures and possible potential benefit in pharmaco resistant seizures.