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Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N ‐methyl‐ D ‐aspartate receptors
Author(s) -
Maskell Peter D,
Speder Pauline,
Newberry Nigel R,
Bermudez Isabel
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705559
Subject(s) - memantine , receptor , nmda receptor , acetylcholine receptor , nicotinic agonist , pharmacology , acetylcholine , chemistry , alpha 4 beta 2 nicotinic receptor , 5 ht2 receptor , cys loop receptors , nicotinic acetylcholine receptor , biochemistry , biology , 5 ht receptor , serotonin
Human α 7 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 125 I‐ α ‐bungarotoxin ( 125 I‐ 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, IC 50 1.7 (−1; +2) μ M , was more potent than memantine, IC 50 5 (−3;+8) μ M , and the effects of both drugs were fully and rapidly reversible. Inhibition of α 7 receptor function was voltage‐independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125 I‐ α ‐bgtx to α 7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. These results provide evidence that human α 7 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