2,3,6-triaminopyridine, a metabolite of the urinary tract analgesic phenazopyridine, causes muscle necrosis and renal damage in rats.
Some aromatic polyamines form very stable free radicals and readily undergo autoxidation with concomitant formation of 'active oxygen' species. These substances cause necrosis of striated muscle in rats, and it has been suggested that this is due to free radical formation and disruption of energy production through their oxidation via the cytochrome c/cytochrome oxidase system of mitochondria. 2,3,6-Triaminopyridine, which is structurally related to the myotoxic amines and likewise undergoes autoxidation and disrupts mitochondrial metabolism, is a metabolite of the widely used urinary analgesic phenazopyridine. When administered to rats, triaminopyridine caused extensive necrosis of skeletal muscle and a lesser degree of damage to heart muscle. It also induced vacuolation and necrosis of distal tubules of the kidney, associated with tubular dilatation and cast formation. Both muscle damage and renal tubular necrosis have been reported following use or abuse of phenazopyridine, and it is likely that triaminopyridine is responsible for both of these effects.
Munday
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AgResearch, Ruakura Agricultural Research Centre, Hamilton, New Zealand. mundayr@agresearch.cri.nz
Manns
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D000779:Anesthetics, Local / Q000633:toxicity; D000818:Animals; D005260:Female; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D010084:Oxidation-Reduction; D010621:Phenazopyridine / Q000378:metabolism; D011725:Pyridines / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
D000779:Anesthetics, Local; D011725:Pyridines; D017382:Reactive Oxygen Species; C089956:2,3,6-triaminopyridine; D010621:Phenazopyridine