Pyrrolylquinoxalinediones: Dicarboxylates as highly potent AMPA receptor antagonists

Pyrrolylquinoxalinediones carrying carboxylates at the pyrrole side-chain were synthesized and evaluated for AMPA receptor binding and for selectivity over other glutamate receptors. Particularly dicarboxy derivatives represent selective and highly potent AMPA antagonists. Moreover, several compounds displayed a remarkable efficacy against AMPA induced lethal convulsions and maximal electroshock seizures (MES) in mice. The good in vivo efficacy of the highly polar compounds suggests the involvement of an active transport mechanism.