Dr. 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 (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.
Penicillamine has been used in rheumatoid arthritis since the first successful case in 1964.
^ abPeisach, J.; Blumberg, W. E. (1969). "A mechanism for the action of penicillamine in the treatment of Wilson's disease". Molecular pharmacology5 (2): 200–209. PMID4306792. edit
^ abRosenberg, L. E.; Hayslett, J. P. (1967). "Nephrotoxic Effects of Penicillamine in Cystinuria". JAMA: the Journal of the American Medical Association201 (9): 698. doi:10.1001/jama.1967.03130090062021.edit
^Steen, V. D.; Medsger Jr, T. A.; Rodnan, G. P. (1982). "D-Penicillamine therapy in progressive systemic sclerosis (scleroderma): A retrospective analysis". Annals of internal medicine97 (5): 652–659. PMID7137731. edit
^Chalmers, A.; Thompson, D.; Stein, H. E.; Reid, G.; Patterson, A. C. (1982). "Systemic lupus erythematosus during penicillamine therapy for rheumatoid arthritis". Annals of internal medicine97 (5): 659–663. PMID6958210. edit
^Bolognia, Jean; et al (2007). Dermatology. Philadelphia: Elsevier. ISBN1-4160-2999-0.2nd edition.