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Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N‐methyl‐D‐aspartate receptors
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Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N‐methyl‐D‐aspartate receptors
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Journal Article
Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N‐methyl‐D‐aspartate receptors
2003
Overview
Human α7 nicotinic acetylcholine (ACh) receptors were expressed in Xenopus oocytes and the effects of the N‐methyl‐D‐aspartate (NMDA) receptor open channel blockers memantine and cerestat on this receptor were examined using two‐electrode voltage‐clamp recordings and 125I‐α‐bungarotoxin (125I‐α‐bgtx) binding. Memantine and cerestat produced complete inhibition of ACh‐induced inward currents with affinities similar to that reported for native NMDA receptors. Cerestat, IC50 1.7 (−1; +2) μM, was more potent than memantine, IC50 5 (−3;+8) μM, and the effects of both drugs were fully and rapidly reversible. Inhibition of α7 receptor function was voltage‐independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I‐α‐bgtx to α7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. These results provide evidence that human α7 receptors are inhibited by memantine and cerestat and suggest that caution should be applied when using these compounds to study systems in which NMDA and nACh receptors co‐exist. British Journal of Pharmacology (2003) 140, 1313–1319. doi:10.1038/sj.bjp.0705559
Publisher
Blackwell Publishing Ltd,Nature Publishing
