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 formation and subsequent lipid peroxidation had been postulated to participate broadly to the pathogenesis of tissue injury, including the brain injury induced by hypoxia, ischemia or trauma, as well as in the physiopathology of chronic neurodegenerative diseases, such as Parkinson's disease. Here we report that dihydroergocryptine protects cultured rat cerebellar granule cells against age-dependent and glutamate-induced neurotoxicity. Dihydroergocryptine antagonizes in fact both the neuronal death produced by acute exposure to a toxic glutamate concentration as well as the normal age-dependent degeneration in culture, presumably by exerting a scavenger action. This effect does not seem mediated entirely by interactions with the dopamine D₂ receptors. The neuroprotective action of dihydroergocryptine suggests a potential usefulness in halting the acute and chronic neurodegenerative diseases related to excitotoxic damage and free radical formation, including Parkinson's disease.