[Tirilazad mesylate (Freedox)--an effective inhibitor of lipid membrane peroxidation]

The 21-aminosteroids (lazaroids) are inhibitors of lipid membrane peroxidation and appear to function as reactive free radical scavengers (RFRS). Freedox--a multimechanistic cytoprotective inhibitor of lipid peroxidation has been developed specifically to minimize secondary tissue damage. It is the first lazaroid compound used in clinical practice for critical care indications. Structurally described as a 21-aminosteroid, it has no glucocorticoid, mineralocorticoid, or other hormonal effects. Cytoprotective pathways of Freedox after its insertion into the lipid bi-layer of cell membrane include: scavenging reactive oxygen intermediates (ROI), stabilizing cell membrane by decreasing fluidity, preserving vitamin E content in membrane, increasing surface viscosity, preserving of post injury Ca+2 homeostasis. There was shown its efficacy in improving neurologic outcome following CNS trauma, subarachnoid hemorrhage, and ischemia. The therapeutic potential of the lazaroid Freedox has been extensively studied in several CNS disorders. There is an increasing experimental and clinical evidence about the oxygen free radical formation and cell membrane lipid peroxidation which play an important role in the pathogenesis of subarachnoid hemorrhage, spinal cord trauma, head injury and inflammatory processes of the NS. Freedox has also been tested in a variety of stroke models. (Fig. 1, Ref. 19.)