Johnson D K, Pippard M J, Murphy T B, Rose N J
J Pharmacol Exp Ther. 1982 May;221(2):399-403.
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.
利用一种新的高灵敏度放射性同位素方法，对与新描述的铁结合药物吡啶醛异烟酰腙相关的螯合剂进行了筛选，以研究它们对大鼠铁排泄的影响。吡啶醛无论是经肠胃外给药还是口服，均能显著促进铁排泄，排泄出的铁与目前用于治疗人类铁过载的药物去铁胺B所利用的铁源相同。吡啶醛的席夫碱衍生物产生了不同程度的铁排泄，其中腙衍生物比单独使用吡啶醛的效果要好得多。这些数据提示了此类药物螯合内源性铁的多种可能机制。吡啶醛苯甲酰腙比等量的母体异烟酰类似物诱导的铁排泄量多约50%，胆汁插管研究表明，这种差异与苯甲酰衍生物作用时间延长有关。静脉注射时，吡啶醛的苯甲酰和异烟酰腙以及水杨醛苯甲酰腙所产生的铁排泄水平均超过等量去铁胺B的水平。得出的结论是，活性席夫碱衍生物的范围可能很广，其中一些（尽管不一定是此处描述的任何特定化合物）可能被证明具有临床应用价值。
