el-Asrar A M, Morse P H, Maimone D, Torczynski E, Reder A T
Department of Ophthalmology, Mansoura University Hospital, Egypt.
Invest Ophthalmol Vis Sci. 1992 Nov;33(12):3463-8.
The protective effect of the anticonvulsant MK-801 and the antitussive dextromethorphan, which are both N-methyl-D-aspartate receptor antagonists, and kynurenic acid, a broad-spectrum excitotoxin antagonist, was tested in cultured rat retinal cells in an hypoxic environment. The protective effect of these antagonists also was tested in cultured retinal cells and in intact adult rat retinas exposed to the exogenous excitotoxins L-glutamic acid and N-methyl-D-aspartic acid. MK-801 and kynurenic acid protected retinal neurons from hypoxic damage and from the toxicity of exogenous L-glutamic acid and N-methyl-D-aspartic acid. Dextromethorphan, a less potent antagonist, did not protect the retinal neurons from hypoxic damage or the toxicity of exogenous L-glutamic acid, but did attenuate N-methyl-D-aspartate toxicity. These results provide evidence that the synaptic release of excitatory transmitters, most likely glutamate and aspartate, mediate the death of hypoxic retinal neurons. Compounds related to MK-801 may have possible therapeutic applications in the management of retinal ischemia.
抗惊厥药MK-801和镇咳药右美沙芬均为N-甲基-D-天冬氨酸受体拮抗剂，广谱兴奋性毒素拮抗剂犬尿氨酸的保护作用，在缺氧环境下的培养大鼠视网膜细胞中进行了测试。这些拮抗剂的保护作用也在培养的视网膜细胞以及暴露于外源性兴奋性毒素L-谷氨酸和N-甲基-D-天冬氨酸的成年大鼠完整视网膜中进行了测试。MK-801和犬尿氨酸可保护视网膜神经元免受缺氧损伤以及外源性L-谷氨酸和N-甲基-D-天冬氨酸的毒性影响。右美沙芬作为一种效力较弱的拮抗剂，不能保护视网膜神经元免受缺氧损伤或外源性L-谷氨酸的毒性影响，但可减轻N-甲基-D-天冬氨酸的毒性。这些结果证明，兴奋性递质（很可能是谷氨酸和天冬氨酸）的突触释放介导了缺氧视网膜神经元的死亡。与MK-801相关的化合物可能在视网膜缺血的治疗中具有潜在的应用价值。
