SYM-2207

A series of substituted 1,2-dihydrophthalazines that potently inhibit AMPA receptor currents has been discovered.Further testing revealed that these compounds are selective, noncompetitive inhibitors that, unlike the 2,3-benzodiazepine GYKI 53655, are inactive at the central benzodiazepine binding site.Compound I inhibited the onset of elec. stimulated seizure activity in an in vivo model.Substitution at the 2-position was found to be crucial for activity.The most potent 1,2-dihydrophthalazine was nearly equipotent to the reported value for GYKI 53655 in its ability to block AMPA currents.