New 7,8-ethylenedioxy-2,3-benzodiazepines as noncompetitive AMPA receptor antagonists.
A series of 1-aryl-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-ones 2a-f, were synthesized and screened as anticonvulsant agents in DBA/2 mice against sound-induced seizures. The new compounds display anticonvulsant properties although the ED(50) values are higher than those of prototypes 1-aryl-3,5-dihydro-7,8-methylenedioxy-4H-2,3-benzodiazepin-4-ones (1) and GYKI 52466, well-known noncompetitive AMPA receptor antagonists. Functional tests were performed to evaluate the antagonistic activity at the AMPA and kainate receptors.
Zappalà
Maria
M
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata 98168, Messina, Italy.
Pellicanò
Alessia
A
Micale
Nicola
N
Menniti
Frank S
FS
Ferreri
Guido
G
De Sarro
Giovambattista
G
Grasso
Silvana
S
De Micheli
Carlo
C
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001667:Binding, Competitive; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008811:Mice, Inbred DBA; D008956:Models, Chemical; D011485:Protein Binding; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000378:metabolism; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D001569:Benzodiazepines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; C061950:GYKI 52466