Antiepileptic effects of tiagabine, a selective GABA uptake inhibitor, in the rat kindling model of temporal lobe epilepsy.
OBJECTIVE
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 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-711) 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 mg/kg 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 mg/kg 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.
Morimoto
K
K
Department of Neuropsychiatry, Faculty of Medicine, Kagawa Medical University, Japan.
Sato
H
H
Yamamoto
Y
Y
Watanabe
T
T
Suwaki
H
H
D000679:Amygdala / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000209:etiology; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D009557:Nipecotic Acids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000078308:Tiagabine; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000927:Anticonvulsants; D002220:Carbamazepine; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D010852:Picrotoxin; D000078308:Tiagabine; D014635:Valproic Acid; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid