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: G C Palmer, E F Cregan, P Bialobok, S G Sydserff, T J Hudzik, D J McCarthy
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 890 Pg. 406-20 ( 1999) ISSN: 0077-8923 [Print] United States
• PMID: 10668446 (Publication Type: Journal Article, Review)

Chemical References

• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• Neuroprotective Agents
• Pyridines
• Receptors, N-Methyl-D-Aspartate
• alpha-phenyl-2-pyridineethanamine dihydrochloride
• N-Methylaspartate

Topics

• Animals
• Cerebral Cortex (drug effects)
• Excitatory Amino Acid Agonists (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology, therapeutic use)
• Hippocampus (drug effects)
• Humans
• Hypoxia (drug therapy)
• Ischemia (drug therapy)
• Mice
• N-Methylaspartate (pharmacology)
• Neuroprotective Agents (blood, pharmacokinetics, therapeutic use)
• Pyridines (blood, pharmacokinetics, therapeutic use)
• Rats
• Rats, Inbred SHR
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)