Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER).
The 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 the hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate.
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Shizuoka, Japan.
T
T
Kanda
M
M
Kurokawa
S
S
Tamura
J
J
Nakamura
A
A
Ishii
Y
Y
Kuwana
T
T
Serikawa
J
J
Yamada
K
K
Ishihara
M
M
Sasa
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D000077236:Topiramate
D000927:Anticonvulsants; D018846:Excitatory Amino Acids; D000077236:Topiramate; D005632:Fructose; D001224:Aspartic Acid; D018698:Glutamic Acid