TY - JOUR
T1 - Novel inhibitors of iron‐dependent lipid peroxidation for neurodegenerative disorders
AU - Hall, Edward D.
PY - 1992
Y1 - 1992
N2 - A considerable body of information supports the occurrence and pathophysiological importance of oxygen radicalmediated lipid peroxidation in acute cerebral damage secondary to traumatic or ischemic injury. Moreover, peroxidative mechanisms have been implicated in chronic neurodegenerative (e.g., Alzheimer's and Parkinson's diseases) and demyelinating (e.g., multiple sclerosis) disorders. Consequently, there has been interest in identification of pharmacological agents with potent ability to interrupt oxygen radical formation or cell membrane lipid peroxidative mechanisms. 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 animal models of brain injury and focal cerebral ischemia. In addition, the compound has been found to attenuate the increased lipid peroxidation observed in Alzheimer's brain tissue, to retard anterograde degeneration of motor nerve fibers, and to be effective in decreasing the clinical disease severity and blood‐brain barrier disruption observed in the multiple sclerosis model of experimental allergic encephalomyelitis. Another series of antioxidants, the 2‐methylaminochromans typified by the compound U‐78517F, have been discovered that are even more potent and effective inhibitors of lipid peroxidation than the 21‐aminosteroids.
AB - A considerable body of information supports the occurrence and pathophysiological importance of oxygen radicalmediated lipid peroxidation in acute cerebral damage secondary to traumatic or ischemic injury. Moreover, peroxidative mechanisms have been implicated in chronic neurodegenerative (e.g., Alzheimer's and Parkinson's diseases) and demyelinating (e.g., multiple sclerosis) disorders. Consequently, there has been interest in identification of pharmacological agents with potent ability to interrupt oxygen radical formation or cell membrane lipid peroxidative mechanisms. 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 animal models of brain injury and focal cerebral ischemia. In addition, the compound has been found to attenuate the increased lipid peroxidation observed in Alzheimer's brain tissue, to retard anterograde degeneration of motor nerve fibers, and to be effective in decreasing the clinical disease severity and blood‐brain barrier disruption observed in the multiple sclerosis model of experimental allergic encephalomyelitis. Another series of antioxidants, the 2‐methylaminochromans typified by the compound U‐78517F, have been discovered that are even more potent and effective inhibitors of lipid peroxidation than the 21‐aminosteroids.
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U2 - 10.1002/ana.410320724
DO - 10.1002/ana.410320724
M3 - Article
C2 - 1510373
AN - SCOPUS:0026659763
SN - 0364-5134
VL - 32
SP - S137-S142
JO - Annals of Neurology
JF - Annals of Neurology
IS - 1 S
ER -