A Comparative Study of the Anticonvulsant Effect of GABA Agonists on Amygdala or Hippocampal Kindled Seizures in Cats

A comparative study of the anticonvulsant effect of GABA agonists on amygdala or hippocampal kindled seizures was performed in cats. Progabide (GABA receptor agonist, 25~100 mg/kg) significantly reduced both the kindled seizure stage and afterdischarge (AD) duration in a dose-dependent manner. SKF89976A (GABA re-uptake inhibitor, 0.25~2 mg/kg) also significantly reduced kindled seizures. At a toxic dose of SKF89976A, induction of the AD in the kindled focus was completely suppressed, although it caused EEG spike and myoclonus. Furthermore, γ-vinyl GABA (GVG: inhibitor of GABA transaminase, 50~200 mg/kg) significantly reduced only the kindled seizure stage with the prolonged duration of ADs. In contrast, baclofen (selective GABA-B receptor agonist, 1 and 5 mg/kg) did not show any anticonvulsant effects either on the seizure stage or on the AD duration. It is concluded that these GABA agonists, which potentiate the inhibitory function of the GABA-A system, have potent anticonvulsant effects on kindled seizures from the lymbic focus as well as secondary generalization in cats.