Penicillamine
Encyclopedia
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.
to treat rheumatoid arthritis
. It works by reducing numbers of T-lymphocyte
s, inhibiting macrophage
function, decreasing IL-1
, decreasing rheumatoid factor
, and preventing collagen
from cross-linking.
It is used as a chelating agent:
, 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.
Chelation therapy
Chelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care in the United States dictates the use of dimercaptosuccinic acid...
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
Pyridoxine
Pyridoxine is one of the compounds that can be called vitamin B6, along with pyridoxal and pyridoxamine. It differs from pyridoxamine by the substituent at the '4' position. It is often used as 'pyridoxine hydrochloride'.-Chemistry:...
). It is a metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
, although it has no antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
properties.
Uses
Penicillamine is used as a form of immunosuppressionImmunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
to treat rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
. It works by reducing numbers of T-lymphocyte
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s, inhibiting macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
function, decreasing IL-1
IL-1
IL-1 may refer to:* Interleukin 1, a protein* Illinois' 1st congressional district* Illinois Route 1* Building 1 of Infinite Loop , the Headquarters of Apple Inc....
, decreasing rheumatoid factor
Rheumatoid factor
Rheumatoid factor is an autoantibody most relevant in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG. RF and IgG join to form immune complexes that contribute to the disease process...
, and preventing collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
from cross-linking.
It is used as a chelating agent:
- In Wilson's diseaseWilson's diseaseWilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease...
, a rare genetic disorder of copperCopperCopper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
metabolism, penicillamine treatment relies on its binding to accumulated copper and elimination through urineUrineUrine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. - In cystinuriaCystinuriaCystinuria is an inherited autosomal recessive disease that is characterized by the formation of cystine stones in the kidneys, ureter, and bladder.-Signs and symptoms:Cystinuria is a cause of persistent kidney stones...
, a hereditary disorder featuring formation of cystineCystineCystine is a dimeric amino acid formed by the oxidation of two cysteine residues that covalently link to make a disulfide bond. This organosulfur compound has the formula 2. It is a white solid, and melts at 247-249 °C...
stones, penicillamine binds with cysteineCysteineCysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
to yield a mixed disulfideDisulfideIn chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms. Disulfide usually refer to a chemical compound that contains a disulfide bond, such as diphenyl disulfide, C6H5S-SC6H5....
which is more soluble than cystine. - Penicillamine has been used to treat sclerodermaSclerodermaSystemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
- Penicillamine is the second line treatment for arsenic poisoning, after dimercaprolDimercaprolDimercaprol or British anti-Lewisite , is a compound developed by British biochemists at Oxford University during World War II. It was developed secretly as an antidote for lewisite, the now-obsolete arsenic-based chemical warfare agent. Today, it is used medically in treatment of arsenic,...
(BAL)
Adverse effects
Adverse effects include:- Membranous glomerulonephritisMembranous glomerulonephritisMembranous glomerulonephritis is a slowly progressive disease of the kidney affecting mostly patients between ages of 30 and 50 years, usually Caucasian.It is one of the more common forms of nephrotic syndrome.-Terminology:...
- Aplastic anemia (idiosyncratic)
- Antibody-mediated myasthenic syndromeLambert-Eaton myasthenic syndromeLambert–Eaton myasthenic syndrome is a rare autoimmune disorder that is characterised by muscle weakness of the limbs...
, which may persist even after its withdrawal - Drug-induced systemic lupus erythematosus
- Elastosis perforans serpiginosa
- Toxic myopathies
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 penicillinPenicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
, and experimentally confirmed that it increased urinary copper excretion by chelation
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
. 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
Dimercaprol
Dimercaprol or British anti-Lewisite , is a compound developed by British biochemists at Oxford University during World War II. It was developed secretly as an antidote for lewisite, the now-obsolete arsenic-based chemical warfare agent. Today, it is used medically in treatment of arsenic,...
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
Triethylene tetramine
Triethylenetetramine, abbreviated TETA and trien, is an organic compound with the formula [CH2NHCH2CH2NH2]2. This oily liquid is colourless but, like many amines, assumes a yellowish color due to impurities resulting from air-oxidation. It is soluble in polar solvents and exhibits the reactivity...
, 2HCl, and tetrathiomolybdate.
External links
- Penicillamine (Systemic) - Medlineplus.org
- Penicillamine and Arthritis - Medicinenet.com