title: 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.
authors.affiliation: Astra Arcus USA, Rochester, New York 14602, USA. eugene.palmer@arcus.us.astra.com
authors.forename: G C
authors.initials: GC
authors.lastname: Palmer
authors.forename: E F
authors.initials: EF
authors.lastname: Cregan
authors.forename: P
authors.initials: P
authors.lastname: Bialobok
authors.forename: S G
authors.initials: SG
authors.lastname: Sydserff
authors.forename: T J
authors.initials: TJ
authors.lastname: Hudzik
authors.forename: D J
authors.initials: DJ
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D007511:Ischemia / Q000188:drug therapy*; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; C096406:alpha-phenyl-2-pyridineethanamine dihydrochloride; D016202:N-Methylaspartate