TY - JOUR T1 - THE DEVELOPMENT OF NEW IRON-CHELATING DRUGS. II JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 757 LP - 765 VL - 205 IS - 3 AU - R. W. GRADY AU - J. H. GRAZIANO AU - G. P. WHITE AU - A. JACOBS AU - A. CERAMI Y1 - 1978/06/01 UR - http://jpet.aspetjournals.org/content/205/3/757.abstract N2 - For the past several years, we have searched for an orally effective iron-chelating drug and report here on several compounds which warrant further investigation based on their ability to promote iron excretion in the hypertransfused rat. Administered orally, 2,3-dihydroxybenzoylglycine induced both urinary and fecal iron excretion, suggesting that a conjugate of 2,3-dihydroxybenzoic acid may be more efficacious than the parent compound. Tropolone, although rather toxic, stimulated fecal excretion of iron when given p.o. at low doses. Evaluation of less toxic derivatives of tropolone appears to be justifiable. L-Histidine may also be of use in chelation therapy. Fecal iron excretion is significantly increased in response to oral doses of this essential amino acid. Lastly, cholylhydroxamic acid proved to be the most efficacious oral agent examined thus far. A marked increase in fecal iron excretion results from its administration. 1978 by the Williams & Wilkins Company ER -