PENICILLAMINE: THE PHARMACOLOGY OF A CHELATING AGENT

Abstract

Penicillamine, dimethyl cysteine, is an amino acid which can be prepared synthetically from valine or by the acid hydrolysis of penicillin. It has an asymmetric carbon atom and can exist in the D, L or DL forms. It possesses a stable -SH group available for complexing or chelating divalent heavy metals, such as copper, mercury, gold and lead. The D isomer is nontoxic to man and has been used effectively in the treatment of Wilson''s disease by depleting copper stores. It can apparently liberate copper from ceruloplasmin, and presumably other copper protein complexes, and renders the metal available for excretion at the glomerulus. It protects rats against experimental HgCl2 poisoning but is less active than the N-acetyl derivative. The L isomer of penicillamine has also been used as a chelating agent but has given rise to toxic reactions[long dash]fever, rashes and granulocytopenia. This is presumably due to its action as an antagonist to pyridoxine (vitamin B6) with which it forms a thiazolidine in vitro, and also presumably in vivo. The use of the D isomer is therefore preferred in clinical practice. Besides its use as a chelating agent penicillamine will also dissociate macroglobulin aggregates thereby reducing serum viscosity in the syndrome of mac roglobulinemia.