The first non-competitive AMPA antagonist GYKI 52466 (Donevan and Rogawski, 1993) was found among a 2,3-benzodiazepine library, a group of compounds known for their anxiolytic and antiepileptic properties (Sólyom and Tarnawa, 2002). GYKI 52466 and structurally-related members that are AMPA/kainate receptor antagonists are currently undergoing clinical trials. For example, Talampanel (GYKI 53773, alternatively named LY300164), a synthetic derivative of dioxolobenzodiazepine, is currently being evaluated for efficacy at reducing symptoms of a variety of neurological conditions such as Parkinson’s (clinical trial Identifiers: NCT00108667; NCT00036296; NCT00696332; NCT00034814). Additionally, perampanel (E2007), a 1,5-substituted bipyridinylone, is a first-in-class, orally administered, and highly selective non-competitive AMPAR antagonist currently undergoing trials for several neurological indications (Identifiers: NCT00505622; NCT00592774; NCT00700310; NCT00699582; NCT00699972; NCT00592904).
