8-Methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e] pyrazine-4-ones: highly in vivo potent and selective AMPA receptor antagonists.
Water soluble 8-methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e]pyraz ine-4-one 4 represents a novel class of highly potent and selective AMPA receptors antagonists with in vivo activity. The dextrorotatory isomer (+)-4 was found to display the highest affinity with an IC50 of 10 nM. It also exhibited very good anticonvulsant effects after i.p., s.c. and i.v. administration in mice subjected to electrical convulsions (MES) and i.p. in audiogenic seizure-e in DBA/2 mice (ED50's < or = 10 mg/kg).
Jimonet
P
P
Aventis Pharma S.A., Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
Chevé
M
M
Bohme
G A
GA
Boireau
A
A
Damour
D
D
Debono
M W
MW
Genevois-Borella
A
A
Imperato
A
A
Pratt
J
J
Randle
J C
JC
Ribeill
Y
Y
Stutzmann
J M
JM
Vuilhorgne
M
M
Mignani
S
S
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008845:Microinjections; D015394:Molecular Structure; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011719:Pyrazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D000927:Anticonvulsants; D007093:Imidazoles; D011719:Pyrazines; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid