It has long been accepted that high concentrations of glutamate can destroy 
neurons, and this is the basis of the theory of excitotoxicity during brain 
injury such as stroke. Glutamate N-methyl-D-aspartate (NMDA) receptor 
antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show 
neuroprotective efficacy in human clinical trials or produced intolerable 
central nervous system adverse effects. The failure of these agents has been 
attributed to poor studies in animal models and to poorly designed clinical 
trials. We also speculate that NMDA receptor antagonism may have hindered 
endogenous mechanisms for neuronal survival and neuroregeneration. It remains to 
be proven in human stroke whether NMDA receptor antagonism can be 
neuroprotective.