Effect of YM872, a selective and highly water-soluble AMPA receptor antagonist, in the rat kindling and rekindling model of epilepsy.
We examined antiepileptogenic and anticonvulsant effects of [2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate (YM872), a potent and highly water-soluble alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor antagonist, in the rat amygdala kindling model of epilepsy. Administration of YM872 significantly suppressed fully kindled seizures. Daily pretreatment with YM872 markedly retarded development of kindling during drug sessions. We also used the rekindling method to investigate the antiepileptogenic effect of YM872 in an attempt to differentiate between true and false effects in the conventional method of daily administration. The results using the rekindling method suggested that the effect of YM872 was truly antiepileptogenic, indicating its possible clinical usefulness as an antiepileptogenic drug. We also affirmed the importance of AMPA receptors in the seizure expression mechanism and development of kindling-induced epileptogenesis.
Hara
Hiroshi
H
Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Okayama City, Okayama 700-8558, Japan.
Yamada
Norihito
N
Kodama
Masazumi
M
Matsumoto
Yosuke
Y
Wake
Yosuke
Y
Kuroda
Shigetoshi
S
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000927:Anticonvulsants; D007093:Imidazoles; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872