Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor 
antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, 
aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in 
clinical trials of stroke or traumatic brain injury. This failure has been 
attributed to the deficient properties of the molecules that entered human 
trials and to inappropriate design of clinical studies. In this article we 
hypothesise that glutamate may be involved in the acute neurodestructive phase 
that occurs immediately after traumatic or ischaemic injury (excitotoxicity), 
but that, after this period, it assumes its normal physiological functions, 
which include promotion of neuronal survival. We propose that NMDA receptor 
antagonists failed stroke and traumatic brain injury trials in human beings 
because blockade of synaptic transmission mediated by NMDA receptors hinders 
neuronal survival.