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• W1651190038 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 Ca 2+ and Na + . In Alzheimer’s 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‐β‐carboline ( 1a ) blocked NMDA receptor–mediated, glutamate‐induced excitotoxicity with an IC 50 value of 27.4 μ m , whereas the closely related 1‐phenyl‐1,2,3,4‐tetrahydro‐β‐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." @default.
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• W1651190038 date "2012-02-01" @default.
• W1651190038 modified "2023-10-16" @default.
• W1651190038 title "1-Benzyl-1,2,3,4-Tetrahydro-β-Carboline as Channel Blocker of N-Methyl-d-Aspartate Receptors" @default.
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• W1651190038 doi "https://doi.org/10.1111/j.1747-0285.2012.01317.x" @default.
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