A derivative of a rigid glutamate analog protects the retina from excitotoxicity.
In the retina, the activation of metabotropic glutamate receptors (mGluRs) reduces the toxic effect of N-methyl-D-aspartate (NMDA). We have induced NMDA-mediated excitotoxicity in the adult rat retina by a single intraocular injection of NMDA. The damage that resulted was estimated by assessing the NMDA-induced loss of retinal choline acetyltransferase (ChAT) activity. The new rigid glutamate analog, dimethyl ester of (+/-)-trans-azetidine-2,4-dicarboxylic acid (t-DMADA), with a putative mGluR-agonistic activity, protected the retina from NMDA-induced loss of ChAT activity. This study demonstrated that t-DMADA can be considered a prototype of new retino-protective agents.
Siliprandi
R
R
Fldia Research Laboratories, Abano Terme, Italy.
Lipartiti
M
M
Fadda
E
E
Arban
R
R
Kozikowski
A P
AP
Manev
H
H
D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005123:Eye; D005971:Glutamates / Q000494:pharmacology*; D007267:Injections; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000187:drug effects; D012164:Retinal Diseases / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*
D005971:Glutamates; D018094:Receptors, Metabotropic Glutamate; C083095:azetidine-2,4-dicarboxylic acid; D001383:Azetidinecarboxylic Acid; D002795:Choline O-Acetyltransferase