Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey.
Glutamatergic excitotoxicity has been implicated as a mechanism for injury in a variety of central nervous system pathologies, including glaucoma. Memantine, an NMDA-type glutamatergic open-channel blocker, has pharmacologic properties that make its efficacy greater under excitotoxic conditions, but lesser under normal conditions. Daily oral dosing for approximately 15 months with 4.0 mg/kg memantine in monkeys yielded plasma concentrations similar to those found in patients who received memantine treatment for Parkinson's disease. This same dose of memantine was not associated with any evidence of an effect on the normal function of the retina and central visual pathways, as indicated by measures of the electroretinogram (ERG) and visually-evoked cortical potential (VECP). Amplitude of the VECP response was reduced in eyes with experimentally induced glaucoma. When compared to vehicle-treated control animals, memantine-treated glaucoma eyes suffered significantly less reduction of VECP amplitude. Preliminary results in a rat model for experimental glaucoma also show that, when compared to control animals, systemic treatment with memantine (10 mg/kg/day) was associated with a significant reduction in glaucoma-induced loss of retinal ganglion cells.
Hare
W
W
Department of Biological Sciences, Allergan, Inc., Irvine, CA 92612, USA. hare_william@allergan.com
WoldeMussie
E
E
Lai
R
R
Ton
H
H
Ruiz
G
G
Feldmann
B
B
Wijono
M
M
Chun
T
T
Wheeler
L
L
D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D007429:Intraocular Pressure; D017075:Laser Coagulation; D008252:Macaca fascicularis; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012449:Safety
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine