Differences in degree of trapping of low-affinity uncompetitive N-methyl-D-aspartic acid receptor antagonists with similar kinetics of block.
Differences in degree of trapping of low-affinity uncompetitive N-methyl-D-aspartic acid receptor antagonists with similar kinetics of block.
复制标题
具有相似阻断动力学的低亲和力非竞争性 N-甲基-D-天冬氨酸受体拮抗剂的捕获程度差异。
DOI：
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复制
发表时间：
1999
影响因子：
3.5
通讯作者：
P. Morley
中科院分区：
文献类型：
--
作者：
G. A. Mealing;T. Lanthorn;C. Murray;D. Small;P. Morley
This study characterizes the trapping of block of N-methyl-D-aspartic acid (NMDA)-induced currents by three structurally distinct, use-dependent NMDA receptor antagonists with similar rapid on-off rates. The antagonism of whole-cell currents in cultured rat cortical neurons by AR-R15896AR, ketamine, and memantine was examined. All three compounds produced a steady-state block after a 30-s coapplication, which was fully relieved after 50 s of NMDA exposure. The amplitudes of block caused by 50 microM AR-R15896AR, 10 microM ketamine, or 10 microM memantine were not significantly different, being 82 +/- 1%, 80 +/- 2%, and 81 +/- 2%, respectively. All three NMDA receptor antagonists exhibited trapping of block that was not significantly increased by extending the agonist/antagonist coapplication beyond 30 s. Although the initial blocks were similar, after 120 s of washout without agonist present, there were significant differences in trapping of block between antagonists, as only 54 +/- 3% of the AR-R15896AR block, 86 +/- 1% of the ketamine block, and 71 +/- 4% of the memantine block remained trapped. The lack of complete trapping is consistent with closed-channel egress by these compounds. Higher antagonist concentrations produced larger initial blocks, but the degree of trapping block was not significantly different from that at lower antagonist concentrations. The results demonstrate that differences in the degree of trapping exist among use-dependent NMDA receptor antagonists even when on and off rates are similar. These differences are correlated with measures of therapeutic index.
DOI：
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发表时间：
1997-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
D. Monaghan;Heidi Larsen
通讯作者：
D. Monaghan;Heidi Larsen
DOI：
10.1073/pnas.85.4.1307
发表时间：
1988-02-01
影响因子：
11.1
作者：
HUETTNER, JE;BEAN, BP
通讯作者：
BEAN, BP
影响因子：
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作者：
KRYSTAL, JH;KARPER, LP;CHARNEY, DS
通讯作者：
CHARNEY, DS