Colchicine
Systematic (IUPAC) name
N-((7S)-5,6,7,9-tetrahydro- 1,2,3,10-tetramethoxy-9- oxobenzo(a)heptalen-7-yl)- acetamide
Identifiers
CAS number	64-86-8
ATC code	M04AC01
PubChem	6167
Chemical data
Formula	C22H25NO6
Mol. weight	399.437
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	X Image File history File links Colchicine_structure. ... IUPAC nomenclature is a systematic way of naming organic chemical compounds. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules . ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Overview of the citric acid cycle The citric acid cycle, one of the central metabolic pathways in aerobic organisms. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...
Legal status	RX/POM The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
Routes	Oral tablets

Colchicine is a highly deadly poisonous alkaloid, originally extracted from plants of the genus Colchicum (Autumn crocus, also known as the "Meadow saffron"). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Its present medicinal use is mainly in the treatment of gout; as well, it is being investigated for its potential use as an anti-cancer drug. It can also be used as initial treatment for pericarditis and preventing recurrences of the condition. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Diagram of Ephedrine An alkaloid, strictly speaking, is a naturally-occurring amine produced by a plant,[1] but amines produced by animals and fungi are also called alkaloids. ... Species See text. ... Binomial name Colchicum autumnale L. Colchicum autumnale, commonly known as autumn crocus, meadow saffron or naked lady, resembles the true crocuses, but flowering in autumn. ... Catharsis is a sudden emotional breakdown or climax that constitutes overwhelming feelings of great pity, sorrow, laughter, or any extreme change in emotion that results in the renewal, restoration and revitalization for living. ... Vomiting (or emesis) is the forceful expulsion of the contents of ones stomach through the mouth. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis. ... Pericarditis is inflammation of the sac surrounding the heart, the pericardium. ...

History

Colchicum extract was first described as a treatment for gout in De Materia Medica by Padanius Dioscorides in the first century CE. Pedanius Dioscorides (ca. ... The Common Era (CE), sometimes known as the Current Era or as the Christian Era, is the period of measured time beginning with the year 1 on the Gregorian calendar. ...

The colchicine alkaloid was first isolated in 1820 by the two French chemists P.S. Pelletier and J. Caventon (Pelletier PS, Caventon J. Ann. Chim. Phys. 1820;14:69). 1820 was a leap year starting on Saturday (see link for calendar). ...

It was later identified as a tricyclic alkaloid, and its pain-relieving and anti-inflammatory effects for gout were linked to its ability to bind with tubulin. Tubulin is the protein which makes up microtubules. ...

Pharmacology

Biological function

Colchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules. Availability of tubulin is essential to mitosis, and therefore colchicine effectively functions as a "mitotic poison" [1]. Since one of the defining characteristics of cancer cells is a significantly increased rate of mitosis, this means that cancer cells are significantly more vulnerable to colchicine poisoning than are normal cells. It should be noted, however, that the therapeutic value of colchicine against cancer is (as is typical with chemotherapy agents) limited by its toxicity against normal cells. Tubulin is the protein which makes up microtubules. ... Microtubules are protein structures found within cells, one of the components of the cytoskeleton. ... Mitosis divides genetic information during cell division. ... Chemotherapy is the use of chemical substances to treat disease. ...

Apart from inhibiting mitosis, a process heavily dependent on cytoskeletal changes, colchicine also inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect. This article or section does not cite its references or sources. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ...

Colchicine as medicine

Colchicine is Food and Drug Administration (FDA)-approved for the treatment of gout and also for familial Mediterranean fever, secondary amyloidosis(AA), and scleroderma. The Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible for regulating food (humans and animal), dietary supplements, drugs (human and animal), cosmetics, medical devices (human and animal) and radiation emitting devices (including non-medical devices), biologics, and... Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder that affects groups of patients originating from around the Mediterranean Sea (hence its name). ... Scleroderma is a rare, chronic disease characterized by excessive deposits of collagen. ...

The Australian biotechnology company Giaconda has developed a combination therapy to treat constipation-predominant irritable bowel syndrome which combines colchicine with the anti-inflammatory drug olsalazine. Giaconda is an Australian biotechnology company headquartered in Sydney. ... Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. ...

Colchicine has a relatively low therapeutic index. The therapeutic index of a medication is a comparison of the amount that causes the therapeutic effect to the amount that causes toxic effects. ...

Side effects

Side effects include gastro-intestinal upset and neutropenia. High doses can also damage bone marrow and lead to anemia. Note that all of these side effects can result from hyper-inhibition of mitosis. It has been suggested that Agranulocytosis be merged into this article or section. ... Grays Anatomy illustration of cells in bone marrow. ... Anemia (AmE) or anaemia (BrE), from the Greek () meaning without blood, refers to a deficiency of red blood cells (RBCs) and/or hemoglobin. ...

Toxicity

Colchicine poisoning has been compared to arsenic poisoning: symptoms start 2 to 5 hours after the toxic dose has been ingested and include burning in the mouth and throat, fever, vomiting, diarrhea, abdominal pain and kidney failure. Death from respiratory failure can follow. There is no specific antidote for colchicine, although various treatments do exist. General Name, Symbol, Number arsenic, As, 33 Chemical series metalloids Group, Period, Block 15, 4, p Appearance metallic gray Atomic mass 74. ... An analogue medical thermometer showing the temperature of 38. ... This article or section does not cite its references or sources. ... Types 5-7 on the Bristol Stool Chart are often associated with diarrhea Diarrhea (in American English) or diarrhoea (in British English) is a generally unpleasant condition in which the sufferer has frequent watery, loose bowel movements (from the ancient Greek word διαρροή = leakage; literally meaning to run through). Acute infectious... Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. ... Renal failure is the condition in which the kidneys fail to function properly. ...

Botanical use

Since chromosome segregation is driven by microtubules, colchicine is also used for inducing polyploidy in plant cells during cellular division by inhibiting chromosome segregation during meiosis; half the resulting gametes therefore contain no chromosomes, while the other half contain double the usual number of chromosomes (i.e., diploid instead of haploid as gametes usually are), and lead to embryos with double the usual number of chromosomes (i.e. tetraploid instead of diploid). While this would be fatal in animal cells, in plant cells it is not only usually well tolerated, but in fact frequently results in plants which are larger, hardier, faster growing, and in general more desirable than the normally diploid parents; for this reason, this type of genetic manipulation is frequent in breeding plants commercially. In addition, when such a tetraploid plant is crossed with a diploid plant, the triploid offspring will be sterile (which may be commercially useful in itself by requiring growers to buy seed from the supplier) but can often be induced to create a "seedless" fruit if pollinated (usually the triploid will also not produce pollen, therefore a diploid parent is needed to provide the pollen). This is the method used to create seedless watermelons, for instance. On the other hand, colchicine's ability to induce polyploidy can be exploited to render infertile hybrids fertile, as is done when breeding triticale from wheat and rye. Wheat is typically tetraploid and rye diploid, with the triploid hybrid infertile. Treatment with colchicine of triploid triticale gives fertile hexaploid triticale. Polyploid (in Greek: πολλαπλόν - multiple) cells or organisms contain more than one copy (ploidy) of their chromosomes. ... Cell division is the process by which a cell (called the parent cell) divides into two cells (called daughter cells). ... Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ... Not to be confused with miosis. ... Gametes, from the ancient Greek γαμετης (spouse), are the specialized germ cells that come together during fertilization (conception) in organisms that reproduce sexually. ... Diploid (meaning double in Greek) cells have two copies (homologs) of each chromosome (both sex- and non-sex determining chromosomes), usually one from the mother and one from the father. ... Haploid (meaning simple in Greek) cells have only one copy of each chromosome. ... Polyploid (in Greek: πολλαπλόν - multiple) cells or organisms contain more than one copy (ploidy) of their chromosomes. ... Polyploid (in Greek: πολλαπλόν - multiple) cells or organisms contain more than one copy (ploidy) of their chromosomes. ... Binomial name Citrullus lanatus (Thunb. ... Triticale Triticale (X Triticosecale) is an artificial hybrid of rye and wheat first bred in laboratories during the late 19th century, but only recently developed into a viable crop. ... Species T. aestivum T. boeoticum T. compactum T. dicoccoides T. dicoccon T. durum T. monococcum T. spelta T. sphaerococcum References:   ITIS 42236 2002-09-22 For the indie rock group see: Wheat (band). ... Binomial name Secale cereale M.Bieb. ... Polyploid (in Greek: πολλαπλόν - multiple) cells or organisms contain more than one copy (ploidy) of their chromosomes. ...

External links

• Feature on colchicine, by Matthew J. Dowd
• Pharmacology of colchicine

• Links to external chemical sources