Flupirtine Partially Prevents Neuronal Injury Induced by Prion Protein Fragment and Lead Acetate

Abstract

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 bothin vitroandin 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 PrP^Scand lead acetate (Pb). These two agents display pleiotropic effects on neurons, which include activation of the NMDA receptor complex. At concentrations above 30 μM the toxic-peptide fragment of PrP^Sccauses apoptotic fragmentation of DNA and is consequently neurotoxic. Pb is neurotoxic at concentrations above 10 μM. Co-administration of flupirtine (10 μM) with either of these agents resulted in reduced neurotoxicity. These data indicate that the cytoprotective effect of flupirtine is measurablein vitroagainst these noxious agents which show their effects, including modulation of the NMDA receptor complex, pleiotropically.