Possible role for memantine in protecting retinal ganglion cells from glaucomatous damage.
Glaucoma is a neurodegenerative disease typified by progressive loss of retinal ganglion cells (RGCs). Mild excitotoxicity has been implicated as one of the factors contributing to RGC death during the glaucomatous process. This type of excitotoxic cell death is due, at least in part, to somewhat excessive activation of N-methyl-D-aspartate (NMDA)-type glutamate receptors. NMDA-receptor activity, however, is also essential for normal neuronal function. This means that potential neuroprotective agents that block virtually all NMDA-receptor activity will have unacceptable clinical side effects. Studies in our laboratory have shown that the adamantane derivative, memantine, blocks only excessive NMDA-receptor activity without disrupting normal activity. Past clinical use has demonstrated that memantine is safe, and it has recently been approved in Europe for the treatment of Alzheimer's disease and vascular dementia. Clinical studies of the safety and efficacy of memantine in glaucoma are currently underway. A series of second-generation memantine derivatives called nitro-memantines are currently in development and may prove to have even greater neuroprotective properties than does memantine.