New GABA-modulating 1,2,4-oxadiazole derivatives and their anticonvulsant activity.

Abstract A series of 3- and 5-aryl-1,2,4-oxadiazole derivatives were prepared and tested for anticonvulsant activity in a variety of models. These 1,2,4-oxadiazoles exhibit considerable activity in both pentylenetetrazole (PTZ) and maximal electroshock seizure (MES) models. Compound 10 was protective in the PTZ model in rats with an oral ED 50 of 25.5 mg/kg and in the MES model in rats with an oral ED 50 of 14.6 mg/kg. Neurotoxicity (rotarod) was observed with an ED 50 of 335 mg/kg. We found several oxadiazoles that acted as selective GABA potentiating compounds with no interaction to the benzodiazepine binding site.