Perhaps the most promising compound from the decahydroisoquinoline family of AMPA/kainate receptor antagonists is tezampanel (NGX424), which has recently been used in a double-blind, placebo controlled, parallel group, multi-center Phase 1 study (Identifier: NCT00567086). Importantly, the ester prodrug of tezampanel (NGX426) is bioavailable after oral administration and has also successfully completed Phase 1 clinical trials (Identifier: NCT00832546). The AMPAR antagonists evaluated in clinical trials appear to be generally well tolerated, with only a few subjects reporting minor side effects such as dry mouth, dizziness and sedation (Gottwald and Aminoff, 2008; Pascuzzi et al., 2009). These early human trials are particularly interesting given that Tezampanel reduced rat cocaine self-administration (Di Ciano and Everitt, 2001).
