The hypothesis that excitoxicity is a mechanism of damage following different types of cerebral injury including global and focal
ischemia (34), and head and
spinal cord trauma (6,7,9,25) has been supported by numerous findings. During
ischemia for example,
glutamate neurotoxicity is mediated in part through
N-methyl-D-aspartate (
NMDA) receptors, since selective antagonists to this receptor protect against hypoxic-ischemic injury (10,35,41). In the last few years, different
NMDA antagonists have been developed and tested; they can be divided into competitive and noncompetitive antagonists. Noncompetitive
NMDA antagonists are extremely lipophilic and reach high levels in the brain after systemic administration. Various studies have demonstrated that these agents provide neuroprotection against hypoxic-ischemic injury (for review see ref. 29). Many competitive
NMDA antagonists are hydrophilic and require direct cerebral administration to obtain high brain levels. Newer competitive
NMDA blockers, such as cis-4-phosphonomethyl-2-piperidine
carboxylic acid (
CGS 19755,
selfotel), provide neuroprotection against global
ischemia, focal
ischemia, and
trauma when given systemically (2,3,32,33).
Selfotel is currently being studied in multicenter safety and efficacy trials for
stroke (17) and
head trauma (6).