Effect of SA4503, a novel σ1 receptor agonist, against glutamate neurotoxicity in cultured rat retinal neurons

We examined the effects of σ1 receptor agonists against glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal rat retinas (16–19 d gestation) were used. The neurotoxic effect of glutamate was quantitatively assessed using the trypan blue exclusion method....

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Published inEuropean journal of pharmacology Vol. 342; no. 1; pp. 105 - 111
Main Authors Senda, Toshihiko, Mita, Shiro, Kaneda, Katsuyuki, Kikuchi, Masashi, Akaike, Akinori
Format Journal Article
LanguageEnglish
Published Amsterdam Elsevier B.V 19.01.1998
Elsevier
Subjects
(+)-Pentazocine
Biological and medical sciences
Glutamate
Medical sciences
Neuropharmacology
Neuroprotective agent
Pharmacology. Drug treatments
Retinal cell culture
SA4503
σ1 Receptor subtype
Retinal cell culture
Glutamate
SA4503
σ1 Receptor subtype
(+)-Pentazocine
Cell culture
Agonist
Rat
Toxicity
Rodentia
Sigma receptor
Central nervous system
Retina
Neuroprotective agent
In vitro
Pentazocine
Vertebrata
Mammalia
Neuron
Animal
Fetus
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Summary:We examined the effects of σ1 receptor agonists against glutamate-induced neurotoxicity in cultured retinal neurons. Primary cultures obtained from fetal rat retinas (16–19 d gestation) were used. The neurotoxic effect of glutamate was quantitatively assessed using the trypan blue exclusion method. A brief exposure of retinal cultures to glutamate (500 μM) led to delayed neuronal cell death. The glutamate-induced neurotoxicity was inhibited by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,b]-cyclohepten-5,10-imine hydrogen maleate (MK-801). The σ1 receptor agonists, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydrochloride (SA4503) and (+)-pentazocine at a concentration range of 0.1~100 μM reduced the glutamate-induced neurotoxicity in a dose-dependent manner. In addition, the neuroprotective effects of both SA4503 and (+)-pentazocine were antagonized by co-treatment with N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a putative σ1 receptor antagonist. These findings suggest that σ1 receptor agonists protect retinal cells against glutamate-induced neurotoxicity.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(97)01450-7