An analysis of the actions of progabide, a specific GABA receptor agonist, on kindling and kindled seizures.

The anticonvulsant properties of the specific GABA receptor agonist, progabide, were evaluated in the kindled amygdaloid seizure model in rats. Progabide attenuated afterdischarge durations and the severity of the accompanying convulsive responses in previously kindled rats. This effect occurred only at doses that also produced sedation and ataxia. When administered daily during kindling acquisition, progabide increased the number of trials necessary to complete kindling. The duration and severity of responses induced by stimulations during the acquisition period were reduced in a dose-dependent manner. In spite of these changes during the acquisition period, all subjects exhibited kindled behavior comparable to that of controls when they had accrued the same total afterdischarge experience. In light of these and other data regarding the GABA system and its influences on kindling, we conclude that GABA acts nonspecifically to attenuate various seizure states. It appears that GABA plays no major role in the mechanisms actually responsible for kindling development.