TY - JOUR
T1 - Effect of YM872, a selective and highly water-soluble AMPA receptor antagonist, in the rat kindling and rekindling model of epilepsy
AU - Hara, Hiroshi
AU - Yamada, Norihito
AU - Kodama, Masazumi
AU - Matsumoto, Yosuke
AU - Wake, Yosuke
AU - Kuroda, Shigetoshi
N1 - Funding Information:
This study was supported by a grant from the Zikei Institute of Psychiatry (S.K.). We thank Astellas Pharma Inc. for kindly supplying YM872.
PY - 2006/2/15
Y1 - 2006/2/15
N2 - 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.
AB - 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.
KW - (Rat)
KW - AMPA receptor antagonists
KW - Epileptogenesis
KW - Kindling
KW - YM872
UR - http://www.scopus.com/inward/record.url?scp=32044440052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32044440052&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2005.11.044
DO - 10.1016/j.ejphar.2005.11.044
M3 - Article
C2 - 16403498
AN - SCOPUS:32044440052
SN - 0014-2999
VL - 531
SP - 59
EP - 65
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -