The low-affinity, use-dependent NMDA receptor antagonist AR-R 15896AR. An update of progress in stroke.
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.
Palmer
G C
GC
Astra Arcus USA, Rochester, New York 14602, USA. eugene.palmer@arcus.us.astra.com
Cregan
E F
EF
Bialobok
P
P
Sydserff
S G
SG
Hudzik
T J
TJ
McCarthy
D J
DJ
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*
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