NR AJJM
AU Perovic,S.; Pergande,G.; Ushijima,H.; Kelve,M.; Forrest,J.; Müller,W.E.G.
TI Flupirtine partially prevents neuronal injury induced by prion protein fragment and lead acetate
QU Neurodegeneration. A Journal for neurodegenerative Disorders, Neuroprotection, and Neuroregeneration 1995 Dec; 4(4): 369-74
PT journal article
AB Flupirtine belongs to the class of triaminopyridines and is successfully applied clinically as a non-opiate analgesic drug with additional muscle relaxant properties. Recently it was reported that flupirtine acts like an antagonist of the N-methyl-D-aspartate (NMDA) receptor complex in neuronal cells both in vitro and in vivo. Here we have used primary cortical cells from rat embryos to demonstrate that this compound is also neuroprotective against the toxic effects caused by the prion agent PrPsc and lead acetate (Pb). These two agents display pleiotropic effects on neurons, which include activation of the NMDA receptor complex. At concentrations above 30 microM the toxic-peptide fragment of PrPsc causes apoptotic fragmentation of DNA and is consequently neurotoxic. Pb is neurotoxic at concentrations above 10 microM. Co-administration of flupirtine (10 microM) with either of these agents resulted in reduced neurotoxicity. These data indicate that the cytoprotective effect of flupirtine is measurable in vitro against these noxious agents which show their effects, including modulation of the NMDA receptor complex, pleiotropically.
IN Der Schmerzmittelwirkstoff Flupirtin aus der Klasse der Triaminopyridine scheint in vitro und in vivo als Antagonist des N-Methyl-D-Aspartat-Rezeptorkomplexes in neuronalen Zellen zu wirken. Eine der Wirkungen von Bleiacetat und proteaseresistenten Prionproteinen auf Neuronen ist eine Aktivierung des N-Methyl-D-Aspartat-Rezeptorkomplexes. Die neurotoxischen Prionproteinfragmente bewirken in Konzentrationen oberhalb von 30 µM eine selbstmörderische DNA-Fragmentierung, während Bleiacetat ab 10 µM neurotoxisch ist. Eine Zugabe von 10 µM Flupitin reduziert diese Neurotoxizität.
ZR 37
MH Amino Acid Sequence; Aminopyridines/*therapeutic use; Analgesics/*therapeutic use; Animal; Cell Survival/drug effects; Cells, Cultured; Cerebral Cortex/cytology/drug effects; Lead; Molecular Sequence Data; Neurons/*drug effects; Neuroprotective Agents/*therapeutic use; Organometallic Compounds/*antagonists & inhibitors; Peptide Fragments/*antagonists & inhibitors; Prions/*antagonists & inhibitors; Rats; Rats, Wistar; Support, Non-U.S. Gov't
AD Abteilung 'Angewandte Molekularbiologie', Institute für Physiologische Chemie, Mainz, Germany.
SP englisch
PO England