Pharmaceutical Chemistry

A common mechanism allows selective targeting of GluN2B subunit-containing N-methyl-D-aspartate receptors

Prof. Dr. Bernhard Wünsch, University of Münster

The N-methyl-D-aspartate (NMDA) receptor is one of the most important Ca2+conductive ion channels in the central nervous system. Malfunction or overactivation of the NMDA receptor leads to serious physiological and cognitive impairments. In particular, the GluN2B subunit-containing NMDA receptor subtype is associated with many neurodegenerative diseases like Huntington’s, Alzheimer’s and Parkinson’s disease. Overactivation of the NMDA receptor leads to high intracellular Ca2+ concentration and subsequently to cell death. With their scientific work the team of Prof. Wünsch identified a general substitution pattern for highly potent GluN2B-selective NMDA receptor antagonists. The resulting “foot-in-the-door” mechanism contributes considerably to the understanding of the gating mechanism of the ligand gated ion channel on the molecular level and represents a valuable starting point for the development of new highly potent drug candidates for the treatment of neurodegenerative diseases.

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