In general, AMPAR antagonists compete with glutamate to prevent AMPAR activation while non-competitive allosteric ligands modulate AMPAR activity at a site distinct from the glutamate binding region. Several, structurally-distinct classes of AMPA antagonists have been described including the quinoxalinediones, isatin oximes, decahydroisoquinolines and isoxazole derivatives (Chimirri et al., 1998; Nikam et al., 1999; Nikam and Kornberg, 2001; Sólyom and Tarnawa, 2002). Historically, these compounds were developed for indications other than substance abuse, but the clinical availability of these compounds provides an exciting opportunity for the treatment of drug addiction.
