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Lazaroids: potent inhibitors of iron-dependent lipid peroxidation for neurodegenerative disorders

  • E. D. Hall
  • J. M. McCall
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

A substantial body of information supports the occurrence and pathophysiological importance of oxygen radical-mediated lipid peroxidation in acute cerebral damage secondary to traumatic or ischemic injury. Moreover, peroxidative mechanisms have been implicated in the chronic neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Consequently, there has been interest in the identification of pharmacological agents with potent ability to interrupt oxygen radical formation or cell membrane lipid peroxidative mechanisms. In this regard, our laboratories have developed a novel series of potent lipid peroxidation inhibitors, known as the 21-aminosteroids or “lazaroids”. One of these compounds, U-74006F or tirilazad mesylate, has shown efficacy in models of brain injury and focal cerebral ischemia. U-74006F has further been observed to antagonize excitotoxic neuronal damage in vitro and in vivo. Additionally, the compound has been found to attenuate the increased lipid peroxidation observed in Alzheimer’s brain tissue, and to retard anterograde degeneration of motor nerve fibers. Another series of antioxidants, the 2-methylaminochromans, typified by the compound U-78517F, has been discovered which are even more potent and effective inhibitors of lipid peroxidation than the 21-aminosteroids.

Keywords

Lipid Peroxidation Focal Cerebral Ischemia Central Nervous System Trauma Multi Lamellar Vesicle Excitotoxic Neuronal Damage 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag/Wien 1993

Authors and Affiliations

  • E. D. Hall
    • 2
  • J. M. McCall
    • 1
  1. 1.CNS Diseases ResearchThe Upjohn CompanyKalamazooUSA
  2. 2.CNS Disease ResearchThe Upjohn CompanyKalamazooUSA

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