THE INHIBITION OF PEROXIDE FORMATION AS A POSSIBLE SUBSTRATE FOR THE NEUROPROTECTIVE ACTION OF DIHYDROERGOCRYPTINE

Dihydroergocryptine is an ergot alkaloid endowed with pharmacological actions mainly related to its dopaminomimetic activity. Free radical f ormation and subsequent lipid peroxidation had been postulated to part ecipate broadly to the pathogenesis of tissue injury, including the br ain injury induced by hypoxia, ischemia or trauma, as well as in the p hysiopathology of chronic neurodegenerative diseases, such as Parkinso n's disease. Here we report that dihydroergocryptine protects cultured rat cerebellar granule cells against age-dependent and glutamate-indu ced neurotoxicity. Dihydroergocryptine antagonizes in fact both the ne uronal death produced by acute exposure to a toxic glutamate concentra tion as well as the normal age-dependent degeneration in culture, pres umably by exerting a scavenger action. This effect does not seem media ted entirely by interactions with the dopamine D-2 receptors. The neur oprotective action of dihydroergocryptine suggests a potential usefuln ess in halting the acute and chronic neurodegenerative diseases relate d to excitotoxic damage and free radical formation, including Parkinso n's disease.