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Colchicine
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| Systematic (IUPAC) name | |
| N-((7S)-5,6,7,9-tetrahydro- 1,2,3,10-tetramethoxy-9- oxobenzo(a)heptalen-7-yl)- acetamide |
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| Identifiers | |
| CAS number | |
| ATC code | M04 |
| PubChem | |
| Chemical data | |
| Formula | C22H25NO6 |
| Mol. mass | 399. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 437 |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
X |
| Legal status |
RX/POM |
| Routes | 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"). In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials 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 The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route A natural product is a Chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical Secondary metabolites are Organic compounds that are not directly involved in the normal growth, development or Reproduction of Organisms Colchicum is a Genus of Flowering plants containing around sixty Species of Perennial plants which grow from Corms It Colchicum autumnale, commonly known as autumn crocus, meadow Saffron or naked lady, is a Flower which resembles the Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Gout (also called metabolic arthritis) is a disease created by a buildup of Uric acid. In medicine a Cathartic is a substance which accelerates Defecation. Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the 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. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled It can also be used as initial treatment for pericarditis and preventing recurrences of the condition. Pericarditis is an Inflammation ( -itis) of the Pericardium (the fibrous sac surrounding the heart In neurons, axoplasmic transport is disrupted by colchicine. Axoplasmic transport, also called axonal transport, is responsible for movement of mitochondria, Lipids Synaptic vesicles Proteins
Contents |
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 (Πεδάνιος Διοσκορίδης ca
The colchicine alkaloid was first isolated in 1820 by the two French chemists P. Year 1820 ( MDCCCXX) was a Leap year starting on Saturday (link will display the full calendar of the Gregorian calendar (or a Leap year S. Pelletier and J. Caventon. [1]
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. A Tubulin is one of several members of a small family of globular Proteins The most common members of the tubulin family are α-tubulin and β-tubulin the proteins that
Pharmacology
Biological function
Colchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules. A Tubulin is one of several members of a small family of globular Proteins The most common members of the tubulin family are α-tubulin and β-tubulin the proteins that Microtubules are one of the components of the Cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers Availability of tubulin is essential to mitosis, and therefore colchicine effectively functions as a "mitotic poison" or spindle poison. Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei These poisons disrupt cellular reproduction by affecting the Protein threads which connect the Centromere regions of Chromosomes known as spindles. [2] 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. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer.
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. Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of White blood cells in humans and form an essential part of the Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens 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. Gout (also called metabolic arthritis) is a disease created by a buildup of Uric acid. Familial Mediterranean fever (FMF is a hereditary inflammatory disorder that affects groups of patients originating from around the Mediterranean Sea (hence In Medicine, amyloidosis refers to a variety of conditions in which Amyloid Proteins are abnormally deposited in organs and/or tissues Scleroderma is a chronic Autoimmune disease characterized by a hardening or Sclerosis in the Skin or other organs It is also used as an anti-inflammatory agent for long-term treatment of Behçet's disease. Behçet disease (Behçet's syndrome Morbus Behçet, silk road disease (bɛˈtʃɛt (enPR bĕCHĔT is a chronic condition due to disturbances in the body’s Immune
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. In Gastroenterology, irritable bowel syndrome ( IBS) is a Functional bowel disorder characterized by mild to severe Abdominal pain, discomfort Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis.
The British drug development company Angiogene is developing a prodrug of colchicine, ZD6126[3] (also known as ANG453) as a treatment for cancer. A prodrug is a pharmacological substance ( drug) that is administered in an inactive (or significantly less active form Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled
Colchicine has a relatively low therapeutic index. The therapeutic index (also known as therapeutic ratio) is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxic
Colchicine is "used widely" off-label by naturopaths for a number of treatments, including the treatment of back pain. Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drug's approved label most often concerning the drug's indication. Naturopathic medicine (also known as naturopathy, or natural medicine) is a Complementary and alternative medicine which emphasizes the body's intrinsic [4]
Side effects
Side effects include gastro-intestinal upset and neutropenia. Neutropenia (adjective neutropenic) from Latin Prefix neutro- and Greek Suffix -πενία (deficiency is High doses can also damage bone marrow and lead to anaemia. Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative 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 kidney failure. Arsenic (ˈɑrsənɪk is a Chemical element that has the symbol As and Atomic number of 33 Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Abdominal pain can be one of the Symptoms associated with transient disorders or serious disease Renal failure or kidney 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 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. Chromosome segregation is a step in cell reproduction or division where chromosomes pair off with their similar homologous chromosome Polyploidy occurs in cells and Organisms when there are more than two homologous sets of Chromosomes. Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. A chromosome is an organized structure of DNA and Protein that is found in cells. In Biology or life science meiosis (pronounced my-oh-sis is a process of reductional division in which the number of chromosomes per cell is cut in half A gamete (from Ancient Greek γαμέτης; translated gamete = wife gametes = husband is a cell that fuses with another gamete e. , diploid instead of haploid as gametes usually are), and lead to embryos with double the usual number of chromosomes (i. "Haplo" redirects here For the fictional character see The Death Gate Cycle. "Haplo" redirects here For the fictional character see The Death Gate Cycle. e. tetraploid instead of diploid). Polyploidy occurs in cells and Organisms when there are more than two homologous sets of Chromosomes. 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). Polyploidy occurs in cells and Organisms when there are more than two homologous sets of Chromosomes. This is the method used to create seedless watermelons, for instance. Watermelon ( Citrullus lanatus ( Thunb) Matsum & Nakai family Cucurbitaceae) refers to both Fruit and Plant of a vine-like (climber 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. Triticale (× Triticosecale) is a hybrid of Wheat ( Triti cum) and Rye ( Se' cale) first bred Wheat ( Triticum spp is a worldwide cultivated grass from the Levant area of the Middle East. Rye ( Secale cereale) is a grass grown extensively as a grain and forage crop Wheat is typically tetraploid and rye diploid, with the triploid hybrid infertile. Treatment with colchicine of triploid triticale gives fertile hexaploid triticale. Polyploidy occurs in cells and Organisms when there are more than two homologous sets of Chromosomes.
When used to induce polyploidy in plants, colchicine is usually applied to the plant as a cream. Polyploidy occurs in cells and Organisms when there are more than two homologous sets of Chromosomes. 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. [5]
References
- ^ Pelletier PS, Caventon J. Ann. Chim. Phys. 1820;14:69
- ^ Cyberbotanica: Colchicine
- ^ Description of ZD6126 on US National Cancer Institute website retrieved 26th April 2008
- ^ "Deaths sound an Rx alert", The Portland Tribune, Apr 20, 2007
- ^ Deppe, Carol (1993). Breed Your own Vegetable Varieties. Little, Brown & Company. p. 150-151. ISBN 0-316-18104-8
External links
- Feature on colchicine, by Matthew J. Dowd at vcu. edu
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