Chemical principles of chelate therapy in neurotoxicology.

The chemical significance of heavy metals in biology arises from their ability to form bonds with metal-binding substances. These bonds are tighter than ordinary ionic bonds and partly of a covalent nature. Metal-binding substances, many of which act by complex formation, play an important role in the regulation of uptake into cells of trace heavy metals. In biology metal-binding substances predominantly act by: Removal of metal ions from cells, i.e. antidotes to mask or remove toxic metal ions that have accidentally been ingested. Imposition of the metal ion into cells in a concentration above normal, e.g. the mechanism of action of many bactericides and fungicides. The fundamental requirements concerning the complex formation capacity of the complexing agent, as well as the toxicity and pharmacokinetics of the complexing agent and complex must be considered before use in medicine as e.g. antidotes. Easily obtained excretion of the complexing agent as well as of the complex is essential to avoid unwanted side effects. The importance of this requirement is demonstrated by alternative treatment regimens in thallotoxicosis.