ANTIEPILEPTIC EFFECTS OF TIAGABINE, A SELECTIVE GABA UPTAKE INHIBITOR, IN THE RAT KINDLING MODEL OF TEMPORAL-LOBE EPILEPSY

Purpose: We determined the antiepileptic profile of tiagabine (TGB), a selective gamma-aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of temporal lobe epilepsy (TLE). Methods: The anticonv ulsant and adverse effects of TGB were examined in amygdala- or hippoc ampal-kindled rats and compared with those of other GABA uptake inhibi tors (SKF89976A and NNC-711) and conventional antiepileptic drugs [AED s: valproate (VPA) and carbamazepine (CBZ)]. Ln addition, the antiepil eptogenic effects of TGB on amygdala kindling development were examine d. Results: TGB (2.5-40 mg/kg intraperitoneally, i.p.) had potent and dose-dependent anticonvulsant effects on both amygdala- and hippocampa l-kindled seizures. The order of anticonvulsant potency of the three G ABA uptake inhibitors tested was: NNC-711 > TGB > SKF-89976A and paral leled the in vitro GABA uptake efficacy. In addition, daily treatment with TGB 10 mg/kg for 10 days significantly retarded kindling developm ent. Although adverse effects of TGB on motor systems were significant ly less than those of VPA and CBZ, high toxic doses of TGB often cause d EEG paroxysm and myoclonus. Conclusions: Our results indicate the cl inical usefulness of TGB for treatment of drug-resistant TLE.