Colchicine

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Colchicine

Colchicine is a highly 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 use is mainly in the treatment of gout.

History

Colchicum extract was first described as a treatment for gout in De Materia Medica by Padanius Dioscorides in the first century CE.

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).

It was later identified as a tricyclic alkaloid and its pain relieving and anti-inflammatory effects for gout were linked to it binding with the protein tubulin.

Pharmacology

Biological function

Colchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules. Apart from inhibiting mitosis, a process heavily dependent on cytoskeletal changes, it also inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect.

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 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.

Side effects

Side-effects include gastro-intestinal upset and neutropenia. Starting the drug early during an attack of gout can exacerbate the symptoms. High doses can also damage bone marrow and lead to anemia. It is not used in the treatment of cancer, as the dose required would lead to intolerable side-effects.

Toxicity

Poisoning resembles intoxication with arsenic: 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, yet treatments do exist.

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.

External links

Feature on colchicine
Pharmacology of colchicine

Alkaloids | Antigout agents

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