Antioxidant action of lazaroids

The role of oxygen free radical-induced lipid peroxidation in the acute pathophysiology of central nervous system (CNS) injury and ischemia has been fairly well established. Thus, efforts have been directed toward the discovery of effective lipid antioxidant compounds that can retard posttraumatic and postischemic neurodegeneration. The 21-aminosteroids, or lazaroids, are a novel series of compounds being developed for the acute treatment of traumatic or ischemic CNS injury; they have been specifically designed to localize within cell membranes and inhibit lipid peroxidation reactions. Lipid peroxidation may play a role in chronic neurodegenerative disorders, and thus these novel lipid antioxidants may find utility in these areas as well. The 21-aminosteroids are the products of an effort to develop nonglucocorticoid steroids that duplicate the cerebroprotective pharmacology of synthetic glucocorticoid steroids. Extensive studies with the glucocorticoid steroid methylprednisolone have indicated that large intravenous doses (30 mg/kg) could ameliorate many of the pathophysiological consequences of traumatic or ischemic injury in the CNS and promote the functional recovery of experimentally injured animals by inhibiting posttraumatic lipid peroxidation.