An in vivo evaluation of iron-chelating drugs derived from pyridoxal and its analogs

Journal Article · Sat May 01 04:00:00 EDT 1982 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6816745

Johnson, D K; Pippard, M J; Murphy, T B; Rose, N J

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.

• Research Organization: Department of Medicine, Division of Hematology, University of Washington, Seattle
• OSTI ID: 6816745
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 221:2; ISSN JPETA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALDEHYDES
ANIMALS
AZINES
BILE
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BODY FLUIDS
CHELATING AGENTS
CLEANING
CLEARANCE
COMPARATIVE EVALUATIONS
DECONTAMINATION
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
EXCRETION
HETEROCYCLIC COMPOUNDS
IN VIVO
IRON
IRON ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MATERIALS
METALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHARMACOLOGY
PYRIDINES
PYRIDOXAL
RATS
RODENTS
TRACER TECHNIQUES
TRANSITION ELEMENTS
VERTEBRATES