PHOSPHONOETHYLPHENYLALANINE DERIVATIVES AS NOVEL ANTAGONISTS OF NON-NMDA IONOTROPIC GLUTAMATE RECEPTORS

Substituted phosphonoethylphenylalanines were evaluated for their ability to antagonize kainic acid (KA)- and AMPA-induced currents in Xenopus oocytes. Compounds which were substituted in the 5-position of the aromatic ring were found to selectively antagonize these currents. In addition, selected members of the series of compounds were demonstrated to possess anticonvulsant activity and to protect against KA-induced striatal toxicity in vivo. The effects of altering the position and identity of the aryl substituents were explored.