2,3-Benzodiazepine AMPA antagonists

The 2,3-benzodiazepine GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylene dioxy-5H-2,3-benzodiazepine) and its analogues represent a family of select ive AMPA antagonists. They modulate AMPA channel functions through an allos teric site on the receptor, which is probably different from the ones invol ved in the actions of cyclothiazide and aniracetam. These compounds are fre quently used as research tools to elucidate glutamate receptor-mediated fun ctions. The most effective members of the family inhibit AMPA-induced curre nts in the submicromolar range. In addition, they are active at low systemi c doses in various in vivo experimental models and also possess a good oral bioavailability. In vitro and in vivo pharmacological results with 2,3-ben zodiazepine AMPA antagonists indicate their potential therapeutical value i n treating a great variety of central nervous system diseases, of which epi lepsy and neurodegenerative disorders are regarded as the most important.