Excitotoxic neuronal death is a phenomenon which is associated with several chronic neurodegenerative conditions (e.g., AIDS-associated dementia, Alzheimer's disease, epilepsy, Parkinson's disease, Huntington's disease, neuropathic pain syndrome, encephalopathy, and other dementias) as well as acute cerebral dysfunctions (e.g., stroke, cerebral ischemia, hypoxia, anoxia, carbon monoxide poisoning and hypoglycemia). Excitotoxic neuronal death is triggered primarily by massive Ca.sup.2+ influx arising from overactivation of glutamate receptor channels of the N-methyl-D-aspartate ("NMDA") subtype (see e.g., "The NMDA Receptor", Collingridge, G. L., ed. (Oxford Univ. Press, 1996); and Lipton and Rosenberg, New Engl. J. Med. (1994) 330:613-22).
Clinical use of existing non-peptidic NMDA specific channel blockers (e.g., phenyclipine (PCP) and dizolcipine (MK-801)) is limited by the frequent occurrence of adverse side effects which impair cognitive functions in treated patients. Clinical use of less specific channel blockers (e.g., dextrorphan and dextromethorphan) is limited by side effects stemming from their interactions with receptors other than NMDA receptors. At present, NMDA-specific peptidic channel blockers are not available.