Antioxidant properties of the triaminopyridine, flupirtine

Flupirtine is a triaminopyridine-derived centrally acting analgesic, which interacts with mechanisms of noradrenergic pain modulation. Recently, it has been found to display neuroprotective effects in various models of excitotoxic cell damage, global and focal ischemia. Although this profile suggests that flupirtine acts as an antagonist of the N-methyl-D-aspartate (NMDA) and glutamate-triggered Ca2+ channel, there is no direct interaction with the receptor. In this paper, we examined whether flupirtine can act as an antioxidant and prevent free radical-mediated structural damage. Flupirtine at 5-30 mu M inhibited ascorbate/Fe2+ (1-10 mu M)-stimulated formation of thiobarbituric reactive substances, an indicator of lipid peroxidation, in rat brain mitochondria. Interestingly, we found an increasing effectiveness of the drug at higher iron concentrations. Additionally, higher concentrations of flupirtine also provided protection against protein oxidation, as demonstrated by a decrease in protein carbonyls formed after treatment of rat brain homogenates with ascorbate/Fe2+. In PC12 cell culture, flupirtine at 10-100 mu M was able to attenuate H2O2-stimulated cell death and improve the survival by 33%. BIOCHEM PHARMACOL 56;10:1323-1329, 1998. (C) 1998 Elsevier Science Inc.