Increase of desensitization as an additional mode of action for classical NMDA receptor channel blockers

被引：1
作者：
Nikolaev M.V. [1 ]
Bolshakov K.V. [1 ]
机构：
[1] Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St.Petersburg, 194223, Pr. Thoreza
来源：
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology | 2010年 / 4卷 / 3期
基金：
俄罗斯基础研究基金会;
关键词：
Desensitization; Ion channel blockade; Memantine; NMDA receptor;
D O I：
10.1134/S1990747810030098
中图分类号：
学科分类号：
摘要：
It is well known that not all effects of such classical NMDA receptor channel blockers as spermine and phylantotoxins are madiated via channel blockade. To determine if these side effects have any functional role we studied inhibition of NMDA receptors by derivatives of phenylcyclohexyl and clinically approved memantine. We showed that these drugs not only blocked the channel pore but also potentiated desensitization of NMDA receptors. Apparently, these effects are not interrelated because there was no correlation between a degree of "trapping" and a level of channel desensitization induced by these blockers. Yet, in contrast to channel blockade, which was strongly voltage-dependent, these compounds affected NMDA receptor desensitization in a voltage-independent manner. Based on these facts, we suppose the existence of two different binding sites for memantine and functionally related compounds, one being responsible for channel blockade and another being coupled to channel desensitization. This possibility should be taken into account when interpreting experimental and clinical effects of these channel blockers. © Pleiades Publishing, Ltd., 2010.
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收藏
页码：302 / 308
页数：6
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