Colchicine 365662 222241539 2008-06-28T08:06:57Z ClueBot 4928500 Reverting possible vandalism by [[Special:Contributions/69.14.121.122|69.14.121.122]] to version by 190.244.159.154. False positive? [[User:ClueBot/FalsePositives|Report it]]. Thanks, [[User:ClueBot]]. (427186) (Bot) {{Drugbox| |IUPAC_name = N-((7S)-5,6,7,9-tetrahydro-<BR>1,2,3,10-tetramethoxy-9-<BR>oxobenzo(a)heptalen-7-yl)-<BR>acetamide | image=Colchicine structure.png | CAS_number=64-86-8 | ATC_prefix=M04 | ATC_suffix=AC01 | ATC_supplemental= | PubChem=6167 | DrugBank= | C=22 | H=25 | N=1 | O=6 | molecular_weight = 399.437 | bioavailability= | metabolism = | elimination_half-life= | excretion = | pregnancy_category = X | legal_status = RX/POM | routes_of_administration= Oral tablets }} '''Colchicine''' is a highly poisonous [[natural product]] and [[secondary metabolite]], originally extracted from plants of the genus ''[[Colchicum]]'' ([[Autumn crocus]], ''Colchicum autumnale'', 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 neurons, [[axoplasmic transport]] is disrupted by colchicine. == History == Colchicum extract was first described as a treatment for gout in ''De Materia Medica'' by [[Dioscorides|Padanius Dioscorides]] in the first century [[Common Era|CE]]. The colchicine alkaloid was first isolated in [[1820]] by the two French chemists P.S. Pelletier and J. Caventon.<ref>Pelletier PS, Caventon J. Ann. Chim. Phys. 1820;14:69</ref> 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]]. == Pharmacology == ===Biological function=== Colchicine inhibits microtubule polymerization by binding to [[tubulin]], one of the main constituents of [[microtubule]]s. Availability of tubulin is essential to [[mitosis]], and therefore colchicine effectively functions as a "mitotic poison" or [[spindle poison]].<ref>[http://biotech.icmb.utexas.edu/botany/colch.html Cyberbotanica: Colchicine<!-- Bot generated title -->]</ref> 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. However, the therapeutic value of colchicine against cancer is (as is typical with [[chemotherapy]] agents) limited by its toxicity against normal cells. Apart from inhibiting mitosis, a process heavily dependent on cytoskeletal changes, colchicine also inhibits [[neutrophil granulocyte|neutrophil]] motility and activity, leading to a net [[inflammation|anti-inflammatory]] effect. Colchicine also inhibits urate crystal deposition, which is enhanced by a low pH in the tissues, probably by inhibiting oxidation of glucose and subsequent lactic acid production in leukocytes. The inhibition of uric acid crystals is a vital aspect on the mechanism of gout treatment. ===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]]. It is also used as an anti-inflammatory agent for long-term treatment of [[Behçet's disease]]. 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]]. The British drug development company [[Angiogene]] is developing a [[prodrug]] of colchicine, [[ZD6126]]<ref>[http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=353153 Description of ZD6126 on US National Cancer Institute website] retrieved 26th April 2008</ref> (also known as ANG453) as a treatment for [[cancer]]. Colchicine has a relatively low [[therapeutic index]]. Colchicine is "used widely" [[off-label]] by [[naturopath]]s for a number of treatments, including the treatment of back pain.<ref>[http://www.portlandtribune.com/news/story.php?story_id=117701511863232000 "Deaths sound an Rx alert"], ''The Portland Tribune'', Apr 20, 2007</ref> ===Side effects=== Side effects include gastro-intestinal upset and [[neutropenia]]. High doses can also damage [[bone marrow]] and lead to [[anaemia]]. Note that all of these side effects can result from hyper-inhibition of mitosis. ===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 [[renal failure|kidney failure]]. Death from respiratory failure can follow. There is no specific antidote for colchicine, although various treatments do exist. ===Botanical use=== Since [[chromosome segregation]] is driven by microtubules, colchicine is also used for inducing [[polyploid]]y in plant cells during [[cellular division]] by inhibiting [[chromosome]] segregation during [[meiosis]]; half the resulting [[gamete]]s 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 frequently used 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 also 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 [[watermelon]]s, 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. When used to induce [[polyploidy]] in plants, colchicine is usually applied to the plant as a cream. It has to be applied to a growth point of the plant, such as an apical tip, shoot or sucker. Seeds can be presoaked in a colchicine solution before planting. As colchicine is so dangerous, it is worth noting that doubling of chromosome numbers can occur spontaneously in nature, and not infrequently. The best place to look is in regenerating tissue. One way to induce it is to chop off the tops of plants and carefully examine the lateral shoots and suckers to see if any look different. <ref>Deppe, Carol (1993). ''Breed Your own Vegetable Varieties''. Little, Brown & Company. p.150-151. ISBN 0-316-18104-8</ref> ==References== {{reflist}} ==External links== *[http://www.phc.vcu.edu/Feature/oldfeature/colchicine/colchicine.html Feature] on colchicine, by Matthew J. Dowd at vcu.edu {{Antigout preparations}} [[Category:Alkaloids]] [[Category:Antigout agents]] [[cs:Kolchicin]] [[de:Colchicin]] [[es:Colchicina]] [[fr:Colchicine]] [[gl:Colquicina]] [[id:Kolkisin]] [[it:Colchicina]] [[ms:Colchicine]] [[nl:Colchicine]] [[ja:コルヒチン]] [[pl:Kolchicyna]] [[pt:Colchicina]] [[ro:Colchicină]] [[ru:Колхицин]] [[fi:Kolkisiini]] [[sr:Колхицин]] [[wa:Coltchicene]] [[zh:秋水仙素]]