NMDA Antagonists – New selective compounds to the NR2B subunit with high affinity
The NMDA receptor, an ion channel consisting of four
protein subunits, is involved in the pathophysiology of chronic neurodegenerative diseases, depression, pain and alcoholism. Different subtypes of NMDA receptors can be categorized based on their subunit composition. The NR2B subunit expression is mostly localized in forebrain regions including cortex, hippocampus and striatum. NR2B-selective antagonists have received considerable attention in recent years as they have shown efficacy in neuroprotection, anti-hyperalgesic and anti-Parkinson animal models. NR2B antagonists bind preferentially to the activated form of the NMDA receptor containing the NR2B subunit and allosterically modulate channel activity by inhibiting channel opening probability. They show advantages over non-selective NMDA receptor antagonists due to greater separation between efficacy and side effects.
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