Colchicine

Colchicine is a kind of alkaloid extracted from the crom or seed of the lily family plants, Colchicum autumnale, and is naturally presented in the Liliaceae Garland and Iphigenia with the contents being 0.11% and 0.1%. It is pale yellow needle crystals. It has slight odor and bitter taste with the melting point being 157 ℃. It is soluble in cold water, alcohol, chloroform and formaldehyde with poor solubility in hot water and is not easily soluble in benzene and ether. It is almost insoluble in petroleum ether with the pH of its 0.5% solution being 5.9. Hydrolysis with ammonia can reduce the toxicity. Colchicine is known to inhibit cell mitosis and has anti-tumor effect. In 1889, Italian scholar Pernice had first discovered the effect of colchicine on mitosis. He had described the metaphase of the lining cells in the stomach and intestines of dogs can be blocked colchicine with spindle being damaged and chromosome action paralyzed as well as a large number of abnormal mitotic cells existing in their metaphase. This abnormal division caused by the colchicine is known as colchicine mitosis (referred as the C mitosis). In the mutagenesis analysis of karyotyping and polyploid, colchicine is a most widely used chemicals. Its water concentration has a positive correlation with its action role. The higher the concentration is, the stronger the effect will be. Various kinds of plants and different organizations are known to have different response to colchicine. Generally, for young and rapidly divided organizations (e.g. germ of germinating seeds), the processing time can be shorter and the concentration should be lower; on the contrary, the processing time can be longer and the concentration should be higher. The effective concentration of colchicine treatment is 0.01 to 0.4% with the concentration of 0.2% having the mostly wide range. For example, if we drop 0.2 to 0.4% of colchicine solution on the diploid watermelon seedlings growing point once a day for four consecutive days, and keep the shade and humidity, you can induce tetraploid watermelon. For cereal crops such as rice, you can have robust seedling with four or more leaves cut an incision in the root neck with the degree within not cutting the growing point and immerse it into the 0.025 to 0.05% colchicine solution, submerge the incision, you can also obtain the tetraploid plants after 8 to 14 days (20 ℃). Currently, the colchicine is widely used for the chromosome doubling for haploid plants obtained from the culture of anther (powder), ovary culture.

Colchicine has a good efficacy in treating acute gout and can quickly relieve pain and can prevent the onset of arthritis with its mechanism of action related to the inhibition of white blood cells and proliferation activities and the effect on lysosomal release.
The pharmacological effects of this product are through reducing activity and phagocytosis of leukocytes in the inflammatory tissue and reducing the inflammation caused by uric acid crystals, and thus playing effects of inflammation, swelling and pain effect, therefore it has selective anti-inflammatory effect on the acute gouty arthritis. In addition the product is also a kind of mitosis toxins with strong inhibitory effect of cell division, making the cells stopped in their division time and leading to tumor cell death, and therefore being used for cancer treatment. This product is easily absorbed after oral administration with 30% binding to plasma proteins and the plasma concentration reaching peak at 0.5 to 2 hours after oral administration. The plasma concentration peak after oral administration of 2mg is about 2.2ng/ml. It can play its efficacy at 12 hours after the administration in the case of acute gout and the efficacy can sustain 50 to 70 hours. The drug concentration in the isolated neutrophils is higher than the plasma concentrations and can maintain for as long as 10 days. This product is mostly metabolized by the liver with the metabolite and the prototype drug being excreted by the bile, further being reabsorbed through the intestinal tract with the unabsorbed part being discharged by the gut. The rest, about 10% to 20%, can be excreted through renal via urine.
This product does not affect the formation, dissolution and excretion of uric acid salt thereby has no effect on lowering the blood uric acid content. It is clinically used for the treatment of acute gouty arthritis attack, prevention of recurrent episodes of acute gouty arthritis, familial Mediterranean fever, leukemia, skin cancer, Hodgkin's disease, and aplastic anemia. It can also applied to the specific treatment of M cycle of various kinds of malignant diseases such as the breast cancer, lung cancer, esophageal cancer, cervical cancer, nasopharyngeal carcinoma, Hodgkin's disease, chronic myelogenous leukemia, and skin cancer.
The above information is edited by the chemicalbook of Dai Xiongfeng.

The adverse reaction has significant correlation with the dosage.
1. Gastrointestinal reactions: nausea, abdominal pain, diarrhea, vomiting and loss of appetite are common early side effects with the incidence being up to 80%. In severe cases, there may be dehydration and electrolyte imbalance. Upon such kind of performance, the drug should be immediately discontinued. Patients of long-term usage can get severe hemorrhagic gastroenteritis or malabsorption syndrome.
2. The blood system reactions: long-term medication can cause agranulocytosis, thrombocytopenia, aplastic anemia, and sometimes threaten the life.
3. Other toxic reactions; it is mainly manifested as urinary tract irritation symptoms such as urinary frequency, urgency, dysuria, hematuria, oliguria, or even renal failure. There may also be symptoms such as stomach, throat or skin burning sensation, and fever, bloody diarrhea, mental changes, myasthenia gravis, and respiratory depression.
4. During the period of taking colchicine, we should pay attention to check blood and liver and kidney function. Patients of hematopoietic dysfunction, liver and kidney damage, heart disease and severe gastrointestinal disease should administer with caution. Pregnant women should be disabled.
5. Muscles, peripheral neuropathy: proximal muscle weakness, and elevated serum creatine kinase; there may also be peripheral nerve axonal polyneuropathy at the same time of damaged muscle cells, manifested as numbness, tingling and weakness; muscle neuropathy is rare, often occurs for people of long-term use in the prevention of gout and those with mild renal insufficiency.

Tablets: 0.5 mg per tablet; injection: 1mg, 2mg.
1. for the treatment of acute gout: for adult who orally administers tablets, apply the first dose of 0.5~1 mg, then take 0.5~0.6 mg every 1 to 2 hours until the joint symptoms or gastrointestinal symptoms get alleviated when you can discontinue the treatment. Usually a total dose of 4~10 mg can play obvious efficacy. Note that the patients should administer the drug as early as possible to get excellent efficacy during the acute phase of medication. If the patients take intravenous injection with the first dose being 1~2mg, slowly inject with 20 mL of saline with the time of being no less than five minutes. If necessary, apply intravenous injection every 6 to 12 hours for 0.5~1 mg until it works with the total dose of 4~5 mg/d. Intravenous injection can give a better efficacy than oral administration, and can also significantly reduce the gastrointestinal reactions.
2. for the prevention of acute gout: Adults should take 0.5~0.6 mg of tablet per time with 2 times daily or intravenous injection of 1~2mg/d. 3. For the diagnosis test of gout: If the acute joints symptom gets alleviated after treatment, this will help confirm the diagnosis.

Colchicine itself has a small toxicity, but after absorption, it can be metabolized (oxidized) in vivo to become the oxydicolchicine of a strong toxicity. It has a strong irritation effect on the digestive tract and can inhibit the blood cells, causing neutropenia deficiency and aplastic anemia. It can also cause paralysis on the nerve center and smooth muscle, resulting in vasodilation, and respiratory center paralysis and death. The human lethal dose of colchicine is 6mg~7mg. Mouse oral-LD ​​was 66.6mg/kg; LD50-intraperitoneal injection of mice is 3.5mg/kg. LD50-subcutaneous injection of rat is 4mg/kg.
This product has been applied for treating acute gout for a long time. Later, it was found that it has a strong inhibitory effect on the cell division. Medically, it has been applied to the treatment of various cancers, such as breast cancer, cervical cancer, esophageal cancer, skin cancer, and chronic myelogenous leukemia. However, due to the high colchicine toxicity, in order to reduce the toxicity and improve the efficacy, people has modified the structure of colchicine with the toxicity of the resulting compounds being reduced, such as colchicine amine (TMCA, I), colchicine methylamine (Demecolcine II), it has now been used clinically.
Colchicine poisoning has a certain incubation period with symptoms often happening at 3d~6d after oral administration or injection. Symptoms include throat burning, nausea, vomiting, abdominal pain, diarrhea, watery stools, hematuria, urine retention, numbness, aching limbs, muscle cramps, hair loss, dilated pupils, and convulsion, paralysis of the central nervous system, and respiratory depression and death. In addition, it can also produce local reactions such as when the drug liquid is leaked out from the blood vessel upon injection, local tissue necrosis can occur. Poisoning is usually caused by ingestion or drug overdose. There are also individual cases in which people take it for suicide. The method of treatment is mainly symptomatic treatment. Patients of swallowing colchicine or patients of colchicine poisoning should be prohibited for the use of oxidants such as potassium permanganate to avoid generating a large number of colchicine oxide in the body which further increases the toxicity.

It is pale yellow crystal or crystalline powder with bitter taste and the color being changed upon exposure to light.. M.p. is 157 ℃ (recrystallized from ethyl acetate), specific rotation [α] 17D-429 ° (1.72%, water),-121° (0.9%, chloroform). It has the maximum absorption wavelengths being 243nm and 350.5 nm in ethanol. This product is easily soluble in water, ethanol and chloroform, soluble in benzene and ether, but insoluble in petroleum ether. The 0.5% solution of this product is acidic. LD50 (mouse, intraperitoneal) is 6.1mg/kg.

It can be used for the study of plant genetics; used as selenium reagent; clinically as anticancer drugs.
The product is a typical mitosis toxin. It can be used for treating acute gout and breast cancer. It can also be used as selenium reagent, for being applied to plant genetics and cancer research.
It is a kind of antineoplastic agents and anti-gout for being used for the treatment acute gout and for the treatment of tumors

• Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset.
• Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis.
• Colchicine should be reserved for patients with insufficient relief, intolerance, or contraindications to NSAIDs.
• The usual oral colchicine dose is 1 mg initially, followed by 0.5 mg every 1 hour until the joint symptoms subside, the patient develops abdominal discomfort or diarrhea, or a total dose of 8 mg has been given.
• IV colchicine should be avoided because it is associated with serious adverse effects (e.g., bone marrow suppression, tissue necrosis from local extravasation, disseminated intravascular coagulation, hepatocellular toxicity, and renal failure). If considered necessary, the recommended initial IV dose is 2 mg (if renal function is normal) diluted in 10 to 20 mL of normal saline administered slowly over 10 to 20 minutes in a secure, freeflowing IV line to avoid extravasation. This may be followed by two additional doses of 1 mg each at 6-hour intervals, with the total dose not exceeding 4 mg. After a full IV course, patients should not receive colchicine by any route for at least 7 days.

This product is a kind of alkaloid extracted from the crom or seed of the lily family plants, Colchicum autumnale. The Colchicum autumnale powder was heated under reflux with 85% ethanol extraction for 4h, the resulted ethanol solution was concentrated under reduced pressure to a semi-gum, dilute with distilled water, with 10% sulfuric acid acidified filtrate with extraction by chloroform, and then concentrate the chloroform extract, the resulted crude colchicine obtained by crystallization was subject to re-crystallization to obtain the finished product. Calculated from the Colchicum autumnale powder, the total yield is 0.15%. In foreign countries, it is mostly extracted from the crom of the Liliaceae Colchicum genus Colchicum bulbs.
Take the bulbs and seeds of Iphigenia indica or Colchicum autumnale as raw material; obtain the final product with ethanol extraction and refining.

toxic substances

toxic

intravenous-rat LD50: 1.6 mg/kg; Oral-Mouse LD50: 5.886 mg/kg

eyes-rabbit 1%/3 days Severe

combustible with fire causing decomposition into toxic nitrogen oxide fumes

warehouse: cold, ventilated and dry; and food raw materials stored separately

Water, carbon dioxide, dry, sandy soil

Colchicine is a pale-yellow powder that is obtained from various species of Colchicum, primarily Colchicum autumnale L. Its total chemical synthesis has been achieved, but the primary source of colchicine currently remains alcohol extraction of the alkaloid from the corm and seed of C. autumnale L. It darkens on exposure to light and possesses

Yellow Solid

Colchicine is a pale yellow powder. It has little or no odor. It darkens on contact with light.

Appearance: colchicine exists in white or light-yellow crystal powder with no smell, and it is seldom prone to absorb moisture. Melting point: it becomes dark when it is exposed to light, and it melts at 87–89?°C. Solubility: this product is soluble in chloroform or ethanol and it dissolves in water. However, the semihydrate crystal can form in certain concentrations. The product is hardly soluble in ether. Specific optical rotation: ?121° (0.9?g/100?mL, chloroform, 589.3?nm, 17?°C).

Meadow saffron (Colchicum) is recorded to treat rheumatic swelling on ancient Egyptian medical papyrus in 1500 B.C.. According to De Materia Medica written by Pedanius Dioscorides in the first century, extract of Meadow saffron is used in treating gout. London Pharmacopoeia in 1618 recorded that colchicine is also applied to treat gout.
In 1820, the ingredient was first isolated by the French chemist P.S. Pelletier and J.B. Caventou. In 1833, it was purified and named by Geiger. Michael Dewar guessed that there are two seven-membered rings in colchicine in 1945. Murray Vernon King et al. determined the structure of colchicine by X-ray diffraction in 1952. In 1959, Albert Eschenmoser integrated the product successfully
Colchicine tablet and raw material are approved mostly in domestic in 2010. The tablet produced by Taiwan manufacturers is approved for being listed in mainland of China in 2012. The raw material made by Indian obtained the approval in 2013. There are three kinds of colchicine approved by FDA: with the combination of probenecid, it is prior to be approved. The others are tablet (2009) and capsule (2014).

anti-inflammatory agent, mitosis inhibitor

In research in plant genetics (for doubling chromosomes).

For treatment and relief of pain in attacks of acute gouty arthritis.

Binds specifically with tubulin thus interfering with microtubule organization.

antimitotic, antigout agent

Colchicine is present in the poisonous autumncrocus (meadow saffron). It is the major alkaloid of Colchicum autumnale L. and Liliaceae. It was used in poison potions in theancient kingdom of Colchis (Greece). It isused therapeutically as an antineoplast, for thesuppression of gout, and in the treatment ofMediterranean fever. It is used in plant studiesfor doubling chromosome groups.

An antimitotic agent that disrupts microtubles by binding to tubulin and preventing its polymerization. Stimulates the intrinsic GTPase activity of tubulin. Induces apoptosis in several normal and t umor cell lines and activates the JNK/SAPK signaling pathway.

colchicine: An alkaloid derivedfrom the autumn crocus, Colchicumautumnale. It inhibits cell division.Colchicine is used in genetics, cytology,and plant breeding research andalso in cancer therapy to inhibit celldivision.

Colchicine, an alkaloid obtained from the autumn crocus, has long been used and is relatively selective for the treatment of acute gouty arthritis. Unlike many of the newer agents for use in gout, colchicine has minimal effects on uric acid synthesis and excretion; it decreases inflammation associated with this disorder. It is thought that colchicine somehow prevents the release of the chemotactic factors and/or inflammatory cytokines from the neutrophils, and this in turn decreases the attraction of more neutrophils into the affected area .The ability of colchicine to bind to leukocyte microtubules in a reversible covalent complex and cause their depolymerization also may be a factor in decreasing the attraction of the motile leukocytes into the inflamed area.

An alkaloid plant hormone.

Acting on polymorphonuclear leukocytes and diminishing phagocytosis, it inhibits the production of lactic acid, causing an increase in the pH of synovial tissue and, thus, a decrease in urate deposition, because uric acid is more soluble at the higher pH. Additionally, colchicine inhibits the release of lysosomal enzymes during phagocytosis that also contributes to the reduction of inflammation. Because colchicine does not lower serum urate levels, it has been found to be beneficial to combine colchicine with a uricosuric agent, particularly probenecid. It is a potent drug, being effective at doses of approximately 1 mg, but doses as small as 7 mg have caused fatalities.

Colchicine is an alkaloid isolated from the dried corns andseeds of Colchicum autumnale L., commonly known as autumncrocus or meadow saffron.It is specifically indicated for acute treatment of goutyarthritis because of its ability to block the production and releaseof the CCF that mediates the inflammatory responsebecause of urate crystals, a mechanism different fromcolchicine’s antimitotic action, which is being investigatedfor its anticancer properties. It is often quite effective inaborting an acute gouty attack if given within the first 10 to12 hours after the onset of arthritis.

Odorless or nearly odorless pale yellow needles or powder that darkens on exposure to light. Used to treat gouty arthritis, pseudogout, sarcoidal arthritis and calcific tendinitis.

Slowly hydrolyzed in acidic solution, but unbuffered solutions are stable at 68°F for at least six months. Isomerizes on exposure to ultraviolet radiation.

Colchicine darkens on exposure to light. Incompatible with strong oxidizing agents. Also incompatible with mineral acids .

As little as 20 mg may be fatal if ingested.

Colchicine is a highly toxic alkaloid. Thetarget organs are the lungs, kidney, gastrointestinal tract, and blood. The toxiceffects include drowsiness, nausea, hypermotility, diarrhea, lowering of body temperature, lowering of blood pressure, tremors,convulsions, and respiratory distress. Chronicingestion may cause aplastic anemia andhemorrhage.
LD50 value, oral (mice): 5.9 mg/kg
Colchicine solution at 10,000 ppm concentration caused severe irritation whenapplied repeatedly to rabbits’ eyes. Colchicine produced teratogenic effects in testanimals. It caused fetal death, cytologicalchanges, and developmental abnormalitiesin hamsters, rabbits, domestic animals,and mice. It tested positive to in vitromammalian nonhuman micronucleus andD. melanogaster — nondisjunction tests formutagenicity (U.S. EPA 1986; NIOSH1986).

Colchicine is classified as super toxic. Probable oral lethal dose in humans is less than 5 mg/kg, i.e. less than 7 drops for a 70 kg (150 lb.) person. Death results from respiratory arrest. The fatal dose varies considerably; as little as 7 mg of Colchicine has proved fatal.

Stable.

Plant-derived alkaloid that binds to tubulin and depolymerizes microtubules.

Colchicine interacts with albumin and binds to tubulin. Its association with tubulin impacts autophagic vacuole fusion with lysosomes. It inhibits tyrosine kinases and phospholipases. Colchicine may be useful for treating acute coronary syndromes. It is prescribed for treating rheumatologic conditions including familial mediterranean fever (FMF) and acute gouty arthritis.

Colchicine is rapidly absorbed after oral administration and tends to concentrate in the spleen, kidney, liver, and gastrointestinal tract. Leukocytes also avidly accumulate and store colchicine even after a single intravenous injection. Since colchicine can accumulate in cells against a concentration gradient, it is postulated that an active transport process may be involved in its cellular uptake. The drug is metabolized, primarily in the liver, by deacetylation. Fecal excretion plays a major role in colchicine elimination, since it and its metabolites are readily secreted into the bile. Only about 15 to 30% of the drug is eliminated in the urine except in patients with liver disease; urinary excretion is more important in these individuals.

The drug can be given intravenously as well as orally, but care must be exercised, since extravasated drug may result in local sloughing of skin and subcutaneous tissues. Relief of pain and inflammation usually occurs within 48 hours. Small doses of colchicine can be used during asymptomatic periods to minimize the reappearance or severity of acute attacks. It should be used with caution in patients with preexisting compromised heart, kidney, gastrointestinal tract, and liver disease. Diarrhea, nausea, vomiting, and abdominal pain are the major limiting side effects that ultimately determine the tolerated dosage. These symptoms occur in approximately 80% of patients who take colchicine, especially in those taking high dosages. The hepatobiliary recycling of colchicine and its antimitotic effect on cells that are rapidly turning over, such as those of the intestinal epithelium, account for its gastrointestinal toxicity. Gastrointestinal symptoms generally intervene before the appearance of more serious toxicity and thereby provide a margin of safety in drug administration. Ingestion of large doses of colchicine may be followed by a burning sensation in the throat, bloody diarrhea, shock, hematuria, oliguria, and central nervous system (CNS) depression.

Colchicine is absorbed on oral administration, with peak plasma levels being attained within 0.5 to 2 hours after dosing. Plasma protein binding is only 31%. It concentrates primarily in the intestinal tract, liver, kidney, and spleen and is excreted primarily in the feces, with only 20% of an oral dose being excreted in the urine. It is retained in the body for considerable periods of time, being detected in the urine and leukocytes for 9 to 10 days following a single dose.

The major use of colchicine is as an antiinflammatory agent in the treatment of acute gouty arthritis; it is not effective in reducing inflammation in other disorders. It also can be used to prevent attacks. Since colchicine is so rapidly effective in relieving the acute symptoms of gout (substantial improvement is achieved within hours), it has been used as a diagnostic aid in this disorder. Therapy with colchicine is usually begun at the first sign of an attack and is continued until symptoms subside, adverse gastrointestinal reactions appear, or a maximum dose of 6 to 7 mg has been reached.

It is a natural toxic secondary metabolite, extracted from Colchicum genus plants. Itprevents gastric cancer by upregulating the dual specificity phosphatase 1 (DUSP1)gene. It is also reported to upregulate transforming growth factor beta 2 (TGF-β2)and A-kinase anchoring protein 12 (AKAP12) in hepatocellular carcinoma (Singhet al. 2016b).

Colchicine may produce bone marrow depression, with long-term therapy resulting in thrombocytopenia or aplastic anemia. At maximum dose levels, GI disturbances (e.g., nausea, diarrhea, and abdominal pain) may occur. Acute toxicity is characterized by GI distress, including severe diarrhea resulting in excessive fluid loss, respiratory depression, and kidney damage. Treatment normally involves measures that prevent shock as well as morphine and atropine to diminish abdominal pain. A number of drug interactions have been reported. In general, the actions of colchicine are potentiated by alkalinizing substances and are inhibited by acidifying drugs, consistent with its mechanism of action of increasing the pH of synovial fluid. Responses to CNS depressants and to sympathomimetic drugs appear to be enhanced. Clinical tests may be affected; most notably, elevated alkaline phosphatase and SGOT (serum glutamate oxaloacetate transaminase) values and decreased thrombocyte values may be obtained.

experimentally by most routes. Human systemic effects: aplastic anemia, blood pressure depression, body temperature decrease, changes in kidney tubules, dyspnea, flaccid paralysis without anesthesia, gastrointestinal effects, kidney damage and hemorrhaging, muscle contraction or spasticity, muscle weakness, nausea or vomiting, respiratory stimulation, and somnolence. An experimental teratogen. Experimental reproductive effects. A severe eye irritant. Human mutation data reported. Inhibits the formation of microtubules and thus impairs cell division. When heated to decomposition it emits toxic fumes of NOx.

Colchicine is a drug used to treat gouty arthritis, pseudogout, sarcoidal arthritis; and calcific tendonitis.

In veterinary medicine, colchicine has been proposed as a treatment in small animals for amyloidosis. For colchicine to be effective, however, it must be given early in the course of the disease and it will be ineffective once renal failure has occurred. At the time of writing, no conclusive evidence exists for its efficacy for this indication in dogs.
Colchicine has also been proposed for treating chronic hepatic fibrosis presumably by decreasing the formation and increasing the breakdown of collagen.

Potentially hazardous interactions with other drugs
Anti-arrhythmics: possible increased risk of toxicity with amiodarone.
Antibacterials: possible increased risk of toxicity with azithromycin, clarithromycin, erythromycin and telithromycin - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure.
Antifungals: possible increased risk of toxicity with itraconazole and ketoconazole - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure.
Antivirals: possible increased risk of toxicity with atazanavir, indinavir, ritonavir and telaprevir - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure.
Calcium-channel blockers: possible increased risk of toxicity with diltiazem and verapamil - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure.
Cardiac glycosides: possible increased risk of myopathy with digoxin.
Ciclosporin: risk of myopathy or rhabdomyolysis, also increased blood-ciclosporin concentrations and nephrotoxicity - suspend or reduce dose of colchicine, avoid concomitant use in renal or hepatic failure.
Grapefruit juice: possible increased risk of toxicity.
Lipid-regulating drugs: possible increased risk of myopathy with fibrates and statins.

This material is an alkaloid. If this chemical getsinto the eyes, remove any contact lenses at once and irrigateimmediately for at least 15 min, occasionally lifting upper andlower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and washimmediately with soap and water. Seek medical attentionimmediately. If this chemical has been inhaled, remove fromexposure, begin rescue breathing (using universal precautions,including resuscitation mask) if breathing has stopped andCPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit. Medicalobservation is recommended for 24-48 h after breathingoverexposure, as pulmonary edema may be delayed. As firstaid for pulmonary edema, a doctor or authorized paramedicmay consider administering a corticosteroid spray.

Colchicine binds to tubulin and prevents its polymerization into microtubules, subsequently disrupting microtubule function. Consequently, it alters nuclear structure, intracellular transport, and cytoplasmic motility, ultimately causing cell death. Colchicine is a potent inhibitor of cellular mitosis.

Metabolism occurs primarily in the liver, with the major metabolite being the amine resulting from amide hydrolysis.

Store at RT

UN1544 Alkaloids, solid, n.o.s. or Alkaloid salts, solid, n.o.s. poisonous, Hazard Class: 6.1; Labels: 6.1- Poisonous materials, Technical Name Required. UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials

Commercial material contains up to 4% desmethylcolchicine. Purify colchicine by chromatography on alumina and eluting with CHCl3 [Ashley & Harris J Chem Soc 677 1944]. Alternatively, an acetone solution on alkali-free alumina has been used, and eluting with acetone [Nicholls & Tarbell J Am Chem Soc 75 1104 1953]. It crystallises as yellow needles from EtOAc or CHCl3 with solvent of crystallisation which can be removed at ~70o. It is soluble in Et2O (0.5%), *C6H6 (1%) and H2O (4%). It is sold as “Colgout” for the treatment of gout and binds to tubulin. [Schreiber et al. Helv Chim Acta 44 540 1961, Scott et al. Tetrahedron 21 3605 1965, van Tamelen et al. Tetrahedron 14 8 1961, Beilstein 14 IV 946.]

No information is currently available on breakdown in soil, groundwater, or surface water. Colchicine alkaloids withstand storage, drying, and boiling.
Ingestion is the most common route of both accidental and intentional exposure to colchicine. It is available as an oral tablet and solution for injection.

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, mineral acids. Keep away from light.

1) Merck 14:2471