Effects of YM90K, a selective AMPA receptor antagonist, on amygdala-kindling and long-term hippocampal potentiation in the rat

Masazumi Kodama, Norihito Yamada, Keiko Sato, Yoshihiro Kitamura, Fumihiko Koyama, Toshiki Sato, Kiyoshi Morimoto, Shigetoshi Kuroda

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

To investigate the role of α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) type glutamate receptors in epileptic seizures, we examined the antiepileptogenic and anticonvulsant effects of YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride], a potent and selective new AMPA receptor antagonist, in the rat amygdala-kindling model of epilepsy. Pretreatment with YM90K (7.5-30 mg/kg i.p.) markedly retarded the evolution of kindling. Once kindling was established, administration of YM90K (7.5-30 mg/kg i.p.) significantly and dose-dependently suppressed fully kindled seizures. The maximal effects were observed 15-30 min after injection. When the intensity of electrical stimulation was increased to twice the generalized seizure-triggering threshold, the anticonvulsant effects of YM90K were reversed, suggesting that they were due to elevation of the generalized seizure-triggering threshold. Furthermore, an anticonvulsant dose (15 mg/kg) of YM90K affected neither field potentials nor long-term potentiation in the hippocampus in vivo. These results indicate that AMPA receptors play an important role in the seizure expression mechanism and the development of kindling-induced epileptogenesis, and suggest the possible clinical usefulness of AMPA receptor antagonists as antiepileptic drugs.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalEuropean Journal of Pharmacology
Volume374
Issue number1
DOIs
Publication statusPublished - Jun 11 1999

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AMPA Receptors
Long-Term Potentiation
Amygdala
Anticonvulsants
Seizures
Epilepsy
Isoxazoles
Glutamate Receptors
Electric Stimulation
6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione
Hippocampus
Injections

Keywords

  • AMPA receptor antagonist
  • Kindling
  • Long-term potentiation
  • YM90K

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Effects of YM90K, a selective AMPA receptor antagonist, on amygdala-kindling and long-term hippocampal potentiation in the rat. / Kodama, Masazumi; Yamada, Norihito; Sato, Keiko; Kitamura, Yoshihiro; Koyama, Fumihiko; Sato, Toshiki; Morimoto, Kiyoshi; Kuroda, Shigetoshi.

In: European Journal of Pharmacology, Vol. 374, No. 1, 11.06.1999, p. 11-19.

Research output: Contribution to journalArticle

Kodama, Masazumi ; Yamada, Norihito ; Sato, Keiko ; Kitamura, Yoshihiro ; Koyama, Fumihiko ; Sato, Toshiki ; Morimoto, Kiyoshi ; Kuroda, Shigetoshi. / Effects of YM90K, a selective AMPA receptor antagonist, on amygdala-kindling and long-term hippocampal potentiation in the rat. In: European Journal of Pharmacology. 1999 ; Vol. 374, No. 1. pp. 11-19.
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