Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, I: Functional measures.
OBJECTIVE
To determine, using electrophysiological measures of visual system function, whether oral daily dosing of memantine is both safe and effective to reduce the injury associated with experimental glaucoma in primates.


METHODS
Argon laser treatment of the anterior chamber angle was used to induce chronic ocular hypertension (COHT) in the right eye of 18 macaque monkeys. Nine animals were orally dosed daily with 4 mg/kg memantine while the other nine animals received an oral dose of vehicle only. Using both conventional and multifocal methods, recordings of the electroretinogram (ERG) were made at approximately 3, 5, and 16 months after elevation of the intraocular pressure (IOP). Recordings of the visually-evoked cortical potential (VECP) were also made at the 16-month time point.


RESULTS
Chronic ocular hypertension was associated with a reduction in the amplitude of components of the multifocal ERG response and visually-evoked cortical potential. Memantine-treated animals suffered less amplitude reduction for these measures than did vehicle-treated animals, though this treatment effect on the ERG measures was observed only at the early time points (3 and 5 months post IOP elevation). Memantine treatment was not associated with an effect on either the kinetics or amplitude of ERG or VECP response measures obtained from the normotensive eyes.


CONCLUSIONS
Systemic treatment with memantine, a compound which does not lower intraocular pressure, was both safe and effective for reduction of functional loss associated with experimental glaucoma.
Hare
William A
WA
Department of Biological Sciences, Allergan Inc., Irvine, California 92612, USA. hare_william@allergan.com
WoldeMussie
Elizabeth
E
Lai
Ronald K
RK
Ton
Hau
H
Ruiz
Guadalupe
G
Chun
Teresa
T
Wheeler
Larry
L
D000284:Administration, Oral; D000818:Animals; D002452:Cell Count; D002908:Chronic Disease; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects*; D005074:Evoked Potentials, Visual / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D007429:Intraocular Pressure; D008252:Macaca fascicularis; D008559:Memantine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000188:drug therapy / Q000503:physiopathology; D009901:Optic Nerve Diseases / Q000188:drug therapy / Q000503:physiopathology; D012160:Retina / Q000187:drug effects / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D012449:Safety; D016896:Treatment Outcome; D014822:Vitreous Body / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D008559:Memantine