Efficacy and safety of memantine, an NMDA-Type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey
Efficacy and safety of memantine, an NMDA-Type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey
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DOI：
10.1016/s0039-6257(01)00200-4
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发表时间：
2001-05-01
影响因子：
5.1
通讯作者：
Wheeler, L
中科院分区：
文献类型：
--
作者：
Hare, W;WoldeMussie, E;Wheeler, L
谷氨酸兴奋性毒性被认为是多种中枢神经系统病变（包括青光眼）损伤的机制。美金刚是所有 NMDA 型谷氨酸开放通道阻滞剂，其药理学特性使其在兴奋性毒性条件下功效更大，但在正常条件下功效较小。猴子每日口服 1.0 mg/kg 美金刚约 15 个月，其血浆浓度与接受美金刚同时治疗帕金森病的患者的血浆浓度相似。视网膜电图（ERG）和视觉诱发皮层电位（VECP）的测量表明，相同剂量的美金刚与对视网膜和中央视觉通路正常功能的影响无关。患有实验性青光眼的眼睛的 VECP 反应幅度降低。与媒介物治疗的对照动物相比，美金刚治疗的青光眼眼睛的 VECP 幅度降低明显较少。实验性青光眼大鼠模型的初步结果还表明，与对照动物相比，美金刚（10 mg/kg/天）全身治疗可显着减少青光眼引起的视网膜神经节细胞损失。 (C) 2001 年，Elsevier Science Inc. 保留所有权利。
Glutamatergic excitotoxicity has been implicated as a mechanism for injury in a variety of central nervous system pathologies, including glaucoma. Memantine, all NMDA-type glutamatergic open-channel blocker, has pharmacologic properties that make its efficacy greater under excitotoxic conditions, bur lesser under normal conditions. Daily oral dosing for approximately 15 months with 1.0 mg/kg memantine in monkeys yielded plasma concentrations similar to those found in patients who received memantime treatment for Parkinson's disease. This same dose of memantine was not associated with by evidence of an effect on the normal function of the retina and central visual pathways, as indicated by measures of the electroretinogram (ERG) and visually-evoked cortical potential (VECP). Amplitude of the VECP response was reduced in eyes with experimentally induced glaucoma. When compared to vehicle-treated control animals, memantine-treated glaucoma eyes suffered significantly less reduction of VECP amplitude. Preliminary results in a rat model for experimental glaucoma also show that, when compared to control animals, systemic treatment with memantine (10 mg/kg/day) was associated with a significant reduction in glaucoma-induced loss of retinal ganglion cells. (C) 2001 by Elsevier Science Inc. All rights reserved.