GABAergic mechanisms in the pathogenesis and treatment of epilepsy.

1. Evidence relating to the role of GABA in the pathogenesis of epilepsy is reviewed. 2. Impaired GABAergic function appears to contribute to seizure susceptibility in a variety of genetically-determined syndromes in animals, e.g. genetically epilepsy prone rats showing sound-induced seizures, gerbils with genetically determined epilepsy, and baboons, Papio papio, with photosensitive epilepsy. 3. In epilepsy secondary to a cerebral insult there is some morphological and biochemical evidence for impaired GABAergic function in experimental situations, but little definitive evidence in man. 4. Pharmacological approaches to enhancing GABAergic inhibition include the use of GABA agonists (or prodrugs), GABA-transaminase inhibition, GABA uptake inhibition, and action at the GABA/benzodiazepine allosteric site. 5. Experimental data suggest that the best prospect for potent anticonvulsant action with fewest side effects (myoclonus, sedation, ataxia) is at present offered by GABA-transaminase inhibitors or novel agents acting on the benzodiazepine receptor site.