Article: Penicillamine

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Penicillamine
Systematic (IUPAC) name
2-amino-3-methyl-3-sulfanyl-butanoic acid
Identifiers
CAS number 52-67-5
ATC code M01CC01
PubChem 5852
DrugBank APRD01171
Chemical data
Formula C5H11NO2S
Mol. weight 149.212 g/mol
Pharmacokinetic data
Bioavailability Variable
Metabolism Hepatic
Half life 1 hour
Excretion Renal
Therapeutic considerations
Pregnancy cat.

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Legal status

Unregulated

Routes  ?

Penicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic (it inhibits the action of pyridoxine). It is a metabolite of penicillin, although it has no antibiotic properties.

Uses

Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. It works by reducing numbers of T-lymphocytes, inhibiting macrophage function, decreasing IL-1, decreasing rheumatoid factor, and preventing collagen from cross-linking.

It is used as a chelating agent:

  • In Wilson's disease, a rare genetic disorder of copper metabolism, penicillamine treatment relies on its binding to accumulated copper and elimination through urine.
  • In cystinuria, a hereditary disorder featuring increased cystine excretion, penicillamine binds with the cystine to make it more soluble.

History

Dr John Walshe (1956) first described the use of penicillamine in Wilson's disease. He had discovered the compound in the urine of patients (including himself) who had taken penicillin, and experimentally confirmed that it increased urinary copper excretion by chelation. He had initial difficulty convincing several world experts of the time (Drs Denny Brown and Cumings) of its efficacy, as they held that Wilson's disease was not primarily a problem of copper homeostasis but of amino acid metabolism, and that dimercaprol should be used as a chelator. Later studies confirmed both the copper-centered theory and the efficacy of D-penicillamine. Walshe also pioneered other chelators in Wilson's such as triethylene tetramine 2HCl and tetrathiomolybdate (Walshe 2003).

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