Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER)
1996; Elsevier BV; Volume: 59; Issue: 19 Linguagem: Inglês
10.1016/0024-3205(96)00492-4
ISSN1879-0631
AutoresTomoyuki Kanda, Masako Kurokawa, Sachiko Tamura, Joji Nakamura, Akio Ishii, Yoshihisa Kuwana, Tadao Serikawa, Junzo Yamada, Kumatoshi Ishihara, Masashi Sasa,
Tópico(s)Pharmacological Effects and Toxicity Studies
ResumoThe spontaneously epileptic rat (SER), a double mutant, manifests both tonic and absence-like seizures. The effect of topiramate, a novel antiepileptic drug, on the extracellular levels of excitatory amino acids (EAA) in the hippocampus of SER was investigated using in vivo microdialysis. The basal levels of glutamate and aspartate in dialysates of hippocampus in SER were 2- to 3-fold higher than those in normal Wistar rats. Both the dose-response relationship and the time course of the suppression of tonic seizures by topiramate were similar to the attenuation of glutamate level in SER. Topiramate (40 mg/kg i.p.) significantly (P < 0.05) reduced both glutamate and aspartate levels in SER while showing no effect on normal Wistar rats. These findings suggest that topiramate reduces abnormally high extracellular levels of glutamate and aspartate in (he hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate.
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