Comparative study of the anticonvulsant effect of gamma-aminobutyric acid agonists in the feline kindling model of epilepsy

Abstract

We made a comparative study of the anticonvulsant effect of GABA agonists on feline amygdala or hippocampal kindled seizures. Progabide (PGB) [gamma-aminobutyric acid (GABA) receptor agonist 25-100 mg/kg intraperitoneally, i.p.] significantly reduced both the kindled seizure stage and after discharge (AD) duration in a dose-dependent manner. SKF89976A (GABA uptake inhibitor 0.5-2.0 mg/kg i.p.) also significantly reduced the kindled seizure stage. Toxic doses of SKF89976A caused generalized paroxysmal EEG discharges and myoclonus, but AD generation in the kindled focus was suppressed completely. Furthermore, gamma-vinyl GABA (GABA catabolic enzyme inhibitor, GVG 50-200 mg/kg i.p.) significantly reduced the seizure stage, while causing prolongation of the AD duration. In contrast, baclofen (selective GABAB receptor agonist, 1 or 5 mg/kg) did not show anticonvulsant effects on any parameters of kindled seizures. Therefore, these GABA agonists, which potentiate the inhibitory function of the GABAA systems, have potent anticonvulsant effects on partial onset and secondarily generalized limbic seizures.