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© Research
Publication : British journal of pharmacology

Inhibition of human alpha 7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in British journal of pharmacology - 01 Dec 2003

Maskell PD, Speder P, Newberry NR, Bermudez I

Link to Pubmed [PMID] – 14645141

Br. J. Pharmacol. 2003 Dec;140(7):1313-9

1. Human alpha 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 125I-alpha-bungarotoxin (125I-alpha-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, IC50 1.7 (-1; +2) microm, was more potent than memantine, IC50 5 (-3;+8) microM, and the effects of both drugs were fully and rapidly reversible. 3. Inhibition of alpha 7 receptor function was voltage-independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I-alpha-bgtx to alpha 7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. 4. These results provide evidence that human alpha 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.

http://www.ncbi.nlm.nih.gov/pubmed/14645141