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Antiepileptic Effects of Tiagabine, a Selective GABA Uptake Inhibitor, in the Rat Kindling Model of Temporal Lobe Epilepsy
Author(s) -
Morimoto Kiyoshi,
Sato Hitoshi,
Yamamoto Yoshitaka,
Watanabe Takemi,
Suwaki Hiroshi
Publication year - 1997
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1997.tb01478.x
Subject(s) - tiagabine , kindling model , anticonvulsant , kindling , epilepsy , pharmacology , carbamazepine , vigabatrin , temporal lobe , amygdala , phenobarbital , chemistry , medicine , psychology , neuroscience
Summary:Purpose: We determined the antiepileptic profile of tiagabine (TGB), a selective γ‐aminobutyric acid (GABA) uptake inhibitor, in the rat kindling model of temporal lobe epilepsy (TLE). Methods : The anticonvulsant and adverse effects of TGB were examined in amygdala‐ or hippocampal‐kindled rats and compared with those of other GABA uptake inhibitors (SKF89976A and NNC‐7 1 1) and conventional antiepileptic drugs [AEDs: valproate (VPA) and carbamazepine (CBZ)]. In addition, the antiepileptogenic effects of TGB on amygdala kindling development were examined. Results : TGB (2.5–40 mgkg intraperitoneally, i.p.) had potent and dose‐dependent anticonvulsant effects on both amygdala‐and hippocampal‐kindled seizures. The order of anticonvulsant potency of the three GABA uptake inhibitors tested was: NNC‐711 > TGB > SKF‐89976A and paralleled the in vitro GABA uptake efficacy. In addition, daily treatment with TGB 10 mgkg for 10 days significantly retarded kindling development. Although adverse effects of TGB on motor systems were significantly less than those of VPA and CBZ, high toxic doses of TGB often caused EEG paroxysm and myoclonus. Conclusions : Our results indicate the clinical usefulness of TGB for treatment of drug‐resistant TLE.