Evaluation of different GABA receptor agonists in the kindled amygdala seizure model in rats.

The effects of three specific GABA receptor agonists, muscimol, progabide, and gaboxadol, on kindled seizures were evaluated in amygdala-kindled rats. The only compound that exerted significant anticonvulsant effects at nonsedative doses was progabide. Thus, after i.p. administration of 100 mg/kg progabide, a significant increase in seizure latency and significant decreases in duration of motor seizures and amygdala afterdischarges were determined. A decrease in severity of motor seizures was found only after 200 mg/kg progabide which, however, gave rise to marked sedation and muscle relaxation. Muscimol and gaboxadol were almost inactive in attenuating kindled seizures even at doses that produced pronounced side effects. Assuming that the amygdala-kindled rat is a useful model of complex partial seizures with secondary generalization in the human, the data suggest that GABA receptor agonists are not effective against this type of epilepsy (muscimol, gaboxadol) or effective only at large doses (progabide).