Efficacy and mechanisms of action of the cytoprotective lipid peroxidation inhibitor tirilazad mesylate in subarachnoid haemorrhage.
Subarachnoid haemorrhage (SAH) following cerebral aneurysm rupture or trauma can result in the induction of secondary ischaemic brain damage via a decrease in microvascular perfusion, a disruption of the blood-brain barrier and consequent vasogenic oedema, and the delayed spasm of the major cerebral arteries (i.e. vasospasm). It is increasingly apparent that oxygen radical-induced, iron-catalyzed lipid peroxidation (LP) within the subarachnoid blood and vascular wall plays a key role in the occurrence of these secondary events. Tirilazad mesylate is a potent cytoprotective inhibitor of LP that works by a combination of radical scavenging and membrane stabilizing properties. It has been demonstrated to attenuate the acute and delayed vascular consequences of SAH and to protect the brain against ischaemic insults. Much of its action is mediated by an effect on the vascular endothelium, although it also appears to exert some direct neuroprotection and to inhibit LP in the subarachnoid blood. These actions of tirilazad in experimental SAH are reviewed.
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CNS Diseases Research, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49001, USA.
D000818:Animals; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000494:pharmacology / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism
D018696:Neuroprotective Agents; D011281:Pregnatrienes; C053355:tirilazad