Generation of superoxide radical and hydrogen peroxide by 2,3,6-triaminopyridine, a metabolite of the urinary tract analgesic phenazopyridine.

2,3,6-Triaminopyridine, a metabolite of the widely-used drug phenazopyridine, has been shown to autoxidize at neutral pH, generating superoxide radical and hydrogen peroxide. Hydrogen peroxide was also detected in erythrocytes exposed to this substance, and these cells suffered oxidative damage, as reflected by methaemoglobin formation and glutathione depletion. The in vitro effects of 2,3,6-triaminopyridine are closely similar to those of the structurally-related compound, 1,2,4-triaminobenzene. The latter substance is known to be highly toxic in vivo by mechanisms which may involve free radical production and oxidative stress. It is possible, therefore, that triaminopyridine may be similarly toxic in animals and that this metabolite could be responsible for some of the harmful side-effects associated with phenazopyridine use.