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Please use this identifier to cite or link to this item: http://dspace.utalca.cl/handle/1950/9085

Title: 1-Benzyl-1,2,3,4-Tetrahydro-ss-Carboline as Channel Blocker of N-Methyl-d-Aspartate Receptors
Authors: Espinoza-Moraga, M.
Caballero, J.
Gaube, F.
Winckler, T.
Santos, L.S.
Keywords: channel blockers
docking; excitotoxicity
NMDA receptor
ss-carboline
Issue Date: Apr-2012
Publisher: WILEY-BLACKWELL, COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
Citation: CHEMICAL BIOLOGY & DRUG DESIGN Volume: 79 Issue: 4 Pages: 594-599 DOI: 10.1111/j.1747-0285.2012.01317.x
Abstract: N-methyl-d-aspartate (NMDA) receptors belong to the family of ligand-gated ion channels and are important for synaptic plasticity and memory function. The NMDA receptor consists of a voltage-dependent channel permeable to Ca2+ and Na+. In Alzheimers disease, neuronal degeneration is thought to cause an excessive release of glutamate to the extracellular space, which may in turn mediate prolonged stimulation of the NMDA receptor complex and, as a consequence, excessive calcium influx into neuronal cells, leading to subsequent cell death. This process is called glutamate-induced excitotoxicity, and its inhibition may present an effective antidementive therapy. We found that 1-benzyl-1,2,3,4-tetrahydro-beta-carboline (1a) blocked NMDA receptormediated, glutamate-induced excitotoxicity with an IC50 value of 27.4 mu m, whereas the closely related 1-phenyl-1,2,3,4-tetrahydro-beta-carboline (1b) had no effect. The binding modes of the reported compounds were studied by in silico docking simulations. We demonstrate that compounds (S)-1a and (R)-1a, but not (S)-1b and (R)-1b, have the same characteristics of potent NMDA receptor blockers, because they establish the main interactions inside the vestibule region of the receptor described previously for the high-affinity NMDA receptor blocker, MK-801.
Description: Reprint Address: Santos, LS (reprint author), Univ Talca, Lab Asymmetr Synth, Chem Inst Nat Resources, POB 747, Talca, Chile.
URI: http://dspace.utalca.cl/handle/1950/9085
ISSN: 1747-0277
Appears in Collections:Artículos en publicaciones ISI - Universidad de Talca

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