Metal binding by pharmaceuticals. Part 4. A comparative investigation of the interaction of metal ions with hydralazine, prizidilol and related compounds.

The metal complexing properties of two antihypertensive drugs, hydralazine (1-hydrazinophthalazine) and prizidilol (a hydrazinopyridazine), and some related ligands, have been studied using potentiometry, elemental analysis, spectrophotometry and computer simulation. The coordination chemistry of 1-hydrazinophthalazine and the hydrazinopyridazines is similar in that Ca(II), Mg(II), and Mn(II) complexes are not formed, whereas Zn(II), Cu(II) and Fe(II)/Fe(III) complexes are produced. Both kinds of ligand react with Fe(II) to form a brightly coloured tetrazene complex which is insoluble for hydralazine but soluble for prizidilol. Computer simulation studies indicate that the most prevalent metal complex of prizidilol in blood plasma is [Fe2+(Priz-)H+]2+ but that this only forms at very high drug concentrations. It is concluded that prizidilol is unlikely to have any direct effects on the metabolism or distribution of the trace elements listed here.