Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors

Peter D. Maskell, Pauline Speder, Nigel R. Newberry, Isabel Bermudez*

*Corresponding author for this work

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

1. 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. 2. 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) μM, was more potent than memantine, IC 50 5 (-3; +8) μM, and the effects of both drugs were fully and rapidly reversible. 3. 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. 4. 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.

Original languageEnglish
Pages (from-to)1313-1319
Number of pages7
JournalBritish Journal of Pharmacology
Volume140
Issue number7
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

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Memantine
Nicotinic Receptors
N-Methyl-D-Aspartate Receptors
Bungarotoxins
Xenopus
Acetylcholine
Oocytes
Electrodes
Pharmaceutical Preparations

Cite this

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title = "Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors",
abstract = "1. 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. 2. 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) μM, was more potent than memantine, IC 50 5 (-3; +8) μM, and the effects of both drugs were fully and rapidly reversible. 3. 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. 4. 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.",
author = "Maskell, {Peter D.} and Pauline Speder and Newberry, {Nigel R.} and Isabel Bermudez",
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Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors. / Maskell, Peter D.; Speder, Pauline; Newberry, Nigel R.; Bermudez, Isabel.

In: British Journal of Pharmacology, Vol. 140, No. 7, 12.2003, p. 1313-1319.

Research output: Contribution to journalArticle

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