The neuroprotective pharmacology of methylprednisolone.
A 24-hour intensive intravenous dosing regimen with the glucocorticoid steroid methylprednisolone has recently been shown to be effective in enhancing neurological recovery in spinal cord-injured patients when initiated within 8 hours after injury. The state of knowledge concerning the neuroprotective pharmacology of methylprednisolone, including mechanism(s) of action, dosing requirements, and time-action considerations is reviewed, as are the results of studies with high doses in experimental and clinical head injury, subarachnoid hemorrhage, and cerebral ischemia. A primary neuroprotective mechanism of action in each of these cases is hypothesized to involve the ability of high doses of methylprednisolone to inhibit oxygen free radical-induced lipid peroxidation, although additional mechanisms may contribute. Unresolved issues are also addressed, including the therapeutic window, optimum duration of treatment, and rational combination with other neuroprotective agents. A newer methylprednisolone pro-drug with improved solution stability is discussed, together with a brief consideration of novel nonglucocorticoid steroids that surpass methylprednisolone's lipid antioxidant effects without unwanted glucocorticoid properties.
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Central Nervous System Diseases Research Unit, Upjohn Company, Kalamazoo, Michigan.
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D006801:Humans; D008775:Methylprednisolone / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D008775:Methylprednisolone