Inhibitors of AMPA and kainate receptors

The glutamate receptor system is implicated in the development and maintena nce of epileptic seizures, and animal studies have disclosed potent anticon vulsant activity of a number of inhibitors of AMPA and/or kainate (KA) rece ptor activity. These results make such inhibitors potential future antiepil eptic drugs. Different series of compounds with inhibitory activity towards AMPA receptors have been developed. Most of these inhibitors are structura lly derived from AMPA, quinoxalinedione or 2,3-benzodiazepine. In contrast, only a limited number of inhibitors of KA receptor activity have been deve loped, most of which contain quinoxalinedione or decahydroisoquinoline skel etons. In spite of promising anticonvulsant activity in various animal mode l studies, no AMPA/KA receptor inhibitors are in clinical use against epile psy today. Based on molecular biology studies, AMPA and KA receptors are at present divided into four and five subtypes, respectively, and attempts to develop subtype selective compounds have been initiated. Future studies an d development of such compounds will indicate whether AMPA/KA receptor inhi bition is a feasible therapeutic strategy for the treatment of epilepsy.