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 phenazopy ridine, has been shown to autoxidize at neutral pH, generating superox ide radical and hydrogen peroxide. Hydrogen peroxide was also detected in erythrocytes exposed to this substance, and these cells suffered o xidative damage, as reflected by methaemoglobin formation and glutathi one depletion. The in vitro effects of 2,3,6-triaminopyridine are clos ely similar to those of the structurally-related compound, 1,2,4-triam inobenzene. The latter substance is known to be highly toxic in vivo b y mechanisms which may involve free radical production and oxidative s tress. It is possible, therefore, that triaminopyridine may be similar ly toxic in animals and that this metabolite could be responsible for some of the harmful side-effects associated with phenazopyridine use.