Radical scavenging action of flunarizine in rat brain in vitro.

In view of recent investigations suggesting that generation of free radicals with subsequent peroxidative disintegration of cellular membranes may be involved in ischemic brain damage, free radical scavenging or antioxidant activity of flunarizine, a calcium-entry blocker with brain protective effects, was investigated in vitro. The experimental systems used were 1) prevention of autoxidation in rat brain homogenate, 2) prevention of lipid peroxidation and swelling induced by Fe2+ and ascorbic acid in rat brain mitochondria, and 3) radical scavenging action against diphenyl-p-picrylhydrazyl, a stable free radical. Although flunarizine was shown to be active in any system, the most pronounced activity of this compound was elicited in the mitochondria, where it was three times greater than that of alpha-tocopherol, a typical intracellular antioxidant. This suggests that the free radical scavenging or antioxidant activity of flunarizine may play a role in its brain protective action.