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The Low‐Affinity, Use‐Dependent NMDA Receptor Antagonist AR‐R 15896AR: An Update of Progress in Stroke

ABSTRACT: Use‐dependent N‐methyl‐d‐aspartate (NMDA) receptor antagonists protect neurons from the lethal consequences of excessive stimulation by excitatory amino acids. Clinical development of high‐affinity compounds such as MK801 have been limited due to untoward side effects. Toward this end, the lower‐affinity use‐dependent NMDA antagonists have greater margins of safety and have advanced to clinical trials for stroke, epilepsy, head trauma and chronic neurodegenerative disorders. AR‐R 15896AR is currently in Phase II trials for stroke and has been repeatedly demonstrated to afford neuroprotection in a variety of in vivo and in vitro models associated with ischemia/excitotoxic conditions.