毒素T3DB ID

T3D2967

目标BioDB ID

BE0000641

目标名称

Glutamate receptor ionotropic, NMDA 3A

目标UniProt ID

Q8TCU5

作用机理

Memantine exerts its action through uncompetitive NMDA receptor antagonism, binding preferentially to the NMDA receptor-operated cation channels. Prolonged increased levels of glutamate in the brain of demented patients are sufficient to counter the voltage-dependent block of NMDA receptors by Mg²⁺ ions and allow continuous influx of Ca²⁺ ions into cells and ultimately neuronal degeneration. Studies suggest that memantine binds more effectively than Mg²⁺ ions at the NMDA receptor, and thereby effectively blocks this prolonged influx of Ca²⁺ ions through the NMDA channel whilst preserving the transient physiological activation of the channels by higher concentrations of synaptically released glutamate. Thus memantine protects against chronically elevated concentrations of glutamate.

参考文献

A1448 - Smothers CT, Woodward JJ: Pharmacological characterization of glycine-activated currents in HEK 293 cells expressing N-methyl-D-aspartate NR1 and NR3 subunits. J Pharmacol Exp Ther. 2007 Aug;322(2):739-48. Epub 2007 May 14. (17502428) A2028 - Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, Shin Y, Cui J, Tu S, Sevarino KA, Nakanishi N, Tong G, Lipton SA, Zhang D: Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature. 2002 Feb 14;415(6873):793-8. Epub 2002 Jan 30. (11823786) A2029 - Schrattenholz A, Soskic V: NMDA receptors are not alone: dynamic regulation of NMDA receptor structure and function by neuregulins and transient cholesterol-rich membrane domains leads to disease-specific nuances of glutamate-signalling. Curr Top Med Chem. 2006;6(7):663-86. (16719808)

创建于

2009-07-22 22:37:10 UTC

更新于

2014-09-04 16:05:16 UTC

目标详情