ABSTRACT
This chapter reviews the pharmacological properties of a novel series of lipid peroxidation (LP) inhibitors, the 21-aminosteroids, that have been shown to be protective in experimental models of acute spinal cord or head injury, focal and global cerebral ischemia, and subarachnoid hemorrhage. Antioxidant doses of methylprednisolone have been shown to be significantly neuroprotective in experimental models of brain and spinal cord injury and in some models of focal cerebral ischemia. The chapter describes two newer classes of lazaroid-type antioxidants, the 2-methylaminochromans and the pyrrolopyrimidines which have improved antioxidant efficacy and brain penetration compared to the 21-aminosteroids. Initial studies of the efficacy of tirilazad in acute head injury demonstrated the ability of the compound to improve early neurological recovery and survival of mice subjected to severe concussive head injury. The cellular mechanism of action of tirilazad in antagonizing posttraumatic ischemia development is believed to involve an inhibition of oxygen radical–mediated microvascular LP.
