Protection by dihydroergocryptine of glutamate-induced neurotoxicity.
Dihydroergocryptine is a hydrogenated ergot derivative with pharmacological actions mainly related to its dopaminomimetic activity. Here we report that dihydroergocryptine can protect cultured rat cerebellar granule cells against glutamate-induced neurotoxicity, assessing cell viability with the fluorescein diacetate-propidium iodide technique. Dihydroergocryptine antagonized both the neuronal death produced by acute exposure to a toxic glutamate concentration as well as the normal age-dependent degeneration in culture. The effect of dihydroergocryptine might be mediated by a scavenger action as suggested by the fact that the compound in a concentration-dependent manner reduced the formation of intracellular peroxides produced in cerebellar granule cells by exposure to 100 microM glutamate. This action is apparently not mediated entirely by interactions with the dopamine D2 receptors. The neuroprotective action suggests that dihydroergocryptine might be a potential useful drug in the therapy and/or prophylaxis of acute and chronic neurodegenerative diseases related to excitotoxic damage.
Favit
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A
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Sortino
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MA
Aleppo
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Scapagnini
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U
Canonico
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PL
D000375:Aging; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects*; D004088:Dihydroergotoxine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists; D005452:Fluoresceins / Q000378:metabolism; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010545:Peroxides / Q000378:metabolism; D011419:Propidium; D051381:Rats
D018691:Excitatory Amino Acid Antagonists; D005452:Fluoresceins; D005971:Glutamates; D010545:Peroxides; D004088:Dihydroergotoxine; D011419:Propidium; D018698:Glutamic Acid; C037631:2',7'-dichlorofluorescein