An in vivo evaluation of iron-chelating drugs derived from pyridoxal and its analogs.
Chelating agents related to the newly described iron binding drug, pyridoxal isonicotinoyl hydrazone, were screened for their effects on iron excretion in the rat, employing a new and highly sensitive radioisotopic procedure. Pyridoxal itself induced significant iron excretion when given either parenterally or orally, the excreted iron being derived from the same pool as that tapped by the drug currently used in treating iron overload in man, desferrioxamine B. Schiff base derivatives of pyridoxal produced varying amounts of iron excretion, the hydrazone derivatives being much more effective than pyridoxal alone. These data suggested a number of possible mechanisms for the chelation of endogenous iron by such agents. Pyridoxal benzoyl hydrazone induced approximately 50% more iron excretion than did an equivalent dose of the parent isonicotinoyl analog and bile cannulation studies showed this difference to be associated with a prolonged duration of action of the benzoyl derivative. When give i.v., the benzoyl and isonicotinoyl hydrazones of pyridoxal and the benzoyl hydrazone of salicylaldehyde all produced levels of iron excretion which exceeded that seen with an equivalent dose of desferrioxamine B. It is concluded that the range of active Schiff base derivatives is likely to be large and that some of these, although not necessarily any of the particular compounds described here, may prove to be of clinical use.
D000818:Animals; D001646:Bile / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D005260:Female; D005293:Ferritins / Q000652:urine; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012545:Schiff Bases / Q000378:metabolism
D002614:Chelating Agents; D007504:Iron Radioisotopes; D012545:Schiff Bases; D011730:Pyridoxal; D005293:Ferritins; D007501:Iron