Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo.
Original spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives were synthesised and led to the identification of 3e which showed good affinities for both the AMPA and the NMDA glycine-site receptors, and displayed good anticonvulsant effects after i.p. and i.v. administrations in the electroshock-induced convulsion assay in mice. The corresponding dextrorotatory isomer (+)-3e was notably more potent than the levorotatory isomer (-)-3e in in vitro and in vivo assays.
Jimonet
P
P
Rhône-Poulenc S.A., Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
Boireau
A
A
Chevé
M
M
Damour
D
D
Genevois-Borella
A
A
Imperato
A
A
Pratt
J
J
Randle
J C
JC
Ribeill
Y
Y
Stutzmann
J M
JM
Mignani
S
S
D000818:Animals; D001665:Binding Sites; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism*; D051379:Mice; D011719:Pyrazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D018691:Excitatory Amino Acid Antagonists; D011719:Pyrazines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D013141:Spiro Compounds; D005998:Glycine