title: Copper chelating agents. A comparison of cupruretic responses to various tetramines and D-penicillamine.
abstract: Toxic or hypersensitivity reactions occur frequently with D-penicillamine therapy. Therefore there is a need for effective, well-tolerated alternative chelating agents to control the copper accumulation which occurs in Wilson's disease and some other chronic liver diseases. A group of tetramines (linear and macrocyclic) was surveyed for cupruretic activity and compared to D-penicillamine. 2,3,2-Tetramine was the most effective agent when given either by gavage or intravenously. It was more effective than 2,2,2-tetramine (trien) or D-penicillamine and, in addition, induced a more prolonged cupruresis. Despite their higher formation constants for copper, the macrocyclic tetramines did not induce a significant cupruresis. In this study, the 2,3,2-tetramine was the most effective agent for inducing a cupruresis in both normal and copper-loaded rats. If well tolerated by humans, it could become a useful agent for management of disorders characterized by copper accumulation.
mesh_terms: D000818:Animals; D002614:Chelating Agents; D003300:Copper / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D006527:Hepatolenticular Degeneration / Q000652:urine; D006801:Humans; D010396:Penicillamine / Q000494:pharmacology* / Q000627:therapeutic use; D011073:Polyamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats
chemical_list: D002614:Chelating Agents; D011073:Polyamines; D003300:Copper; D010396:Penicillamine