A novel adamantane derivative attenuates retinal ischemia-reperfusion damage in the rat retina through sigma1 receptors.
The effects of a novel N-methyladamantan-1-amine derivative [(-)-MR22] with high sigma1 receptor affinity were investigated on retinal degeneration using a rat model of ischemia-reperfusion injury. The animals were anaesthetized and retinal ischemia was induced by elevating the intraocular pressure to 120 mm Hg for 45 min. The drug was injected intraperitoneally before the ischemic damage. Retinal biochemical changes, i.e. increase of lactate content and decrease of glucose and ATP were significantly inhibited by the new and selective sigma1 receptor ligand compared to the ischemic control group. The effect of (-)-MR22 was antagonized by pre-treatment with the sigma1 site antagonist. The protective effect of (-)-MR22 on ischemic retina was confirmed by the histological analysis. These findings suggest that (-)-MR22 serves as a retinal neuroprotective agent and acts as a sigma1 receptor agonist.
Bucolo
Claudio
C
Department of Experimental and Clinical Pharmacology, School of Medicine, University of Catania, Catania, Viale A. Doria 6, I-95125 Catania, Italy. bucocla@unict.it
Marrazzo
Agostino
A
Ronsisvalle
Simone
S
Ronsisvalle
Giuseppe
G
Cuzzocrea
Salvatore
S
Mazzon
Emanuela
E
Caputi
Achille
A
Drago
Filippo
F
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015427:Reperfusion Injury / Q000150:complications*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D000840:Anisoles; C511973:MR22 compound; D011437:Propylamines; D017480:Receptors, sigma; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D000218:Adamantane