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

• Published in: British journal of pharmacology Vol. 140; no. 7; pp. 1313 - 1319
• Main Authors: Maskell, Peter D, Speder, Pauline, Newberry, Nigel R, Bermudez, Isabel
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2003; Nature Publishing
• Subjects: Biological and medical sciences; cerestat; Medical sciences; memantine; Nicotinic acetylcholine receptors; NMDA receptor open channel blockers; Pharmacology. Drug treatments; Human; Glutamate receptor; Antiparkinson agent; Cholinergic receptor; Memantine; NMDA receptor open channel hlockers; α7 nicotinic receptor; Nicotinic acetylcholine receptors; Neurotransmitter; Acetylcholine; Antagonist; NMDA receptor; Nicotinic receptor; cerestat
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705559

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