Penicillamine, sold under the trade names of Cuprimine among others, is a medication primarily used for treatment of Wilson's disease, cystinuria and active rheumatoid arthritis. Penicillamine is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of penicillamine. Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between penicillamine and cystine, resulting in formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cystine and is excreted readily. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity.

Bucillamine [SA96:N-(2-mercapto-2-methylpropanoyl)-L-cysteine] is a synthetic SH compound and an antirheumatic agent developed from tiopronin. It is mainly used in Japan and Korea. Activity is mediated by the two thiol groups that the molecule contains. Research done in the USA showed positive transplant preservation properties. Bucillamine has the potential to attenuate or prevent damage during myocardial infarction, cardiac surgery and organ transplantation. Bucillamine is a more potent thiol donor than other cysteine derivatives: approximately 16-fold more potent than N-acetylcysteine (Mucomyst(R)) in vivo. In addition bucillamine appears to have additional anti-inflammatory effects unrelated to its antioxidant effect. Oral bucillamine is used clinically in Asia for treatment of rheumatoid arthritis. There is a strong preclinical evidence that parenteral infusion of this agent is efficacious in acute settings characterized by inflammation and oxidative stress. In Phase I human trials healthy volunteers received bucillamine at doses up to 25 mg/kg/h i.v. for 3 h and elicited no serious toxicity. On the basis of pharmacokinetic analyses of blood levels during these studies, it was concluded that bucillamine infused at i.v. doses > or =10 mg/kg/h for 3 h to humans could be expected to be therapeutically effective in myocardial infarction, organ transplantation and other acute inflammatory syndromes. Bucillamine exhibits potent antioxidant activity similar to those of trolox and ascorbic acid. It reduces the stable free radical diphenyl-2-picrylhydrazyl (DPPH). Bucillamine is a potent antioxidant which exerts its beneficial therapeutic activities in RA patients by metal chelation rather than by scavenging free radical species.

Trientine, also known as triethylenetatramine or abbreviation TETA, is a highly selective divalent Cu(II) chelator and orphan drug that reverses copper overload in tissues. It was approved as second-line pharmacotherapy for Wilson's disease. Wilson's disease (hepatolenticular degeneration) is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper but when their capacity is exceeded copper is released into the blood and is taken up into extrahepatic sites. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body. Although penicillamine treatment is believed to be more extensive, TETA therapy has been shown to be an effective initial therapy. In addition, TETA is in a clinical trial phase II for the prevention of the Macular Edema after Cataract Surgery. TETA is also considered a potential chemotherapeutic agent as it could be a telomerase inhibitor. Chelating excess copper may affect copper-induced angiogenesis. Other mechanisms of action of TETA for alternative therapeutic implications include improved antioxidant defense against oxidative stress, pro-apoptosis, and reduced inflammation.

Trientine, also known as triethylenetatramine or abbreviation TETA, is a highly selective divalent Cu(II) chelator and orphan drug that reverses copper overload in tissues. It was approved as second-line pharmacotherapy for Wilson's disease. Wilson's disease (hepatolenticular degeneration) is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper but when their capacity is exceeded copper is released into the blood and is taken up into extrahepatic sites. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body. Although penicillamine treatment is believed to be more extensive, TETA therapy has been shown to be an effective initial therapy. In addition, TETA is in a clinical trial phase II for the prevention of the Macular Edema after Cataract Surgery. TETA is also considered a potential chemotherapeutic agent as it could be a telomerase inhibitor. Chelating excess copper may affect copper-induced angiogenesis. Other mechanisms of action of TETA for alternative therapeutic implications include improved antioxidant defense against oxidative stress, pro-apoptosis, and reduced inflammation.