Barbiturates as protective agents in brain ischemia and as free radical scavengers in vitro

Barbiturates protect the brain in several types of ischemia. The exact mechanism(s) by which they afford protection are unknown. Interest has been focused for the most part on their effects as metabolic depressants, but a slowing energy consumption rate in the ischemic brain cannot explain protection in all ischemic situations. Other propositions for the protective mechanisms of barbiturates include alterations in blood flow distribution, membrane stabilization as well as antioxidant and free radical scavenging properties. We have studied the inhibitory effects of various barbiturates on iron- and ascorbic acid-stimulated lipid peroxidation in brain tissue in vitro. While thiopental was highly efficient, other barbiturates had no (phenobarbital, pentobarbital) or only minor (methohexital) inhibitory effects. The findings were confirmed by studies of the scavenging properties of these barbiturates with a different system (1,1 diphenyl-2-picryl hydrazyl). Since all tested barbiturates protect in brain ischemia in vivo, our results do not support the hypothesis that they protect by acting as free radical scavengers.