title: 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.
abstract: 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).
authors.affiliation: Aventis Pharma S.A., Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
authors.forename: P
authors.initials: P
authors.lastname: Jimonet
authors.forename: M
authors.initials: M
authors.lastname: Chevé
authors.forename: G A
authors.initials: GA
authors.lastname: Bohme
authors.forename: A
authors.initials: A
authors.lastname: Boireau
authors.forename: D
authors.initials: D
authors.lastname: Damour
authors.forename: M W
authors.initials: MW
authors.lastname: Debono
authors.forename: A
authors.initials: A
authors.lastname: Genevois-Borella
authors.forename: A
authors.initials: A
authors.lastname: Imperato
authors.forename: J
authors.initials: J
authors.lastname: Pratt
authors.forename: J C
authors.initials: JC
authors.lastname: Randle
authors.forename: Y
authors.initials: Y
authors.lastname: Ribeill
authors.forename: J M
authors.initials: JM
authors.lastname: Stutzmann
authors.forename: M
authors.initials: M
authors.lastname: Vuilhorgne
authors.forename: S
authors.initials: S
authors.lastname: Mignani
mesh_terms: 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
chemical_list: 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