Пеницилламин: Химиялық құрамы, қолданылуы және Уилсон ауруындағы ролі

Chemical compound

Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease.

Penicillamine is a trifunctional organic compound, consisting of a thiol, an amine, and a carboxylic acid. It is an amino acid structurally similar to cysteine, but with geminal dimethyl substituents α to the thiol. Like most amino acids, it is a colorless solid that exists in the zwitterionic form at physiological pH. Penicillamine is a chiral drug with one stereogenic center; the two enantiomers have distinctly different physiological effects. (S) penicillamine (D penicillamine, having (–) optical rotation) is antiarthritic. (R) penicillamine (L penicillamine, having (+) optical rotation) is toxic because it inhibits the action of pyridoxine (also known as vitamin B6). That enantiomer is a metabolite of penicillin but has no antibiotic properties itself. A variety of penicillamine–copper complex structures are known.

John Walshe first described the use of penicillamine in Wilson's disease in 1956. 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 (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 and tetrathiomolybdate. Penicillamine was first synthesized by John Cornforth under supervision of Robert Robinson. Penicillamine has been used in rheumatoid arthritis since the first successful case in 1964.

In the United States, Valeant raised the cost of the medication from about US$500 to US$24,000 per month in 2016.