Chelating drugs and zinc.

Essential trace metals participate in a wide range of biochemical processes. Administration of drugs containing nucleophilic atoms, primarily N-, O- and S-ligands, may result in formation of organometallic non-ionic complexes or chelates. The stability of the complex depends on the position of the metal in the first transition series, except for Cu2+, which forms stronger bindings than Zn2+ does. In nature, a wide range of chelates occur, e.g. as vitamin-metal complexes (Zn-thiamine, Zn-pyridoxamine and Zn-biotin). Phytate in unleavened grains forms unsoluble Zn-complexes. In the body, complex-formation is essential for the transport of Zn with circulating plasma albumin. Some examples of chelating drugs are given. Zn-pyrithione is used for local treatment of dandruff and pityrosporum folliculitis. Ethambutol is a strong metal-binding drug used for tuberculosis therapy. The mechanism of action is possibly related to inactivation of Zn and Cu in the pathogenic organisms. 8-hydroxyquinolines enhance Zn absorption, which is the reason for the successful treatment of acrodermatitis enteropathica. Effects of D-penicillamine, phenytoin, tetracycline and disulfiram on Zn metabolism are discussed.