Possible Role for Memantine in Protecting Retinal Ganglion Cells from Glaucomatous Damage

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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Survey of Ophthalmology Elsevier

Possible Role for Memantine in Protecting Retinal Ganglion Cells from Glaucomatous Damage

Survey of Ophthalmology, Volume 48 (2) – Apr 1, 2003

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Publisher
Elsevier
Copyright
Copyright © 2003 Elsevier Science Inc.
ISSN
0039-6257
D.O.I.
10.1016/S0039-6257(03)00008-0
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Survey of OphthalmologyElsevier

Published: Apr 1, 2003

References

  • The mode of action of antagonists of the excitatory response to acetylcholine in aplysia neurones
    Ascher, P.; Marty, A.; Neild, T.O.
  • Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells
    Ascher, P.; Large, W.A.; Rang, H.P.
  • Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey
    Hare, W.; WoldeMussie, E.; Lai, R.
  • Neuroprotective therapy
    Hickenbottom, S.L.; Grotta, J.
  • Molecular basis of glutamate toxicity in retinal ganglion cells
    Sucher, N.J.; Lipton, S.A.; Dreyer, E.B.
  • Memantine in severe dementia
    Winblad, B.; Poritis, N.
  • Nitrate therapy may retard glaucomatous optic neuropathy, perhaps through modulation of glutamate receptors
    Zurakowski, D.; Vorerk, C.K.; Gorla, M.

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