Definition
A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE).
Description
Colchicine is only found in individuals that have used or taken this drug. It is a major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). The precise mechanism of action has not been completely established. In patients with gout, colchicine apparently interrupts the cycle of monosodium urate crystal deposition in joint tissues and the resultant inflammatory response that initiates and sustains an acute attack. Colchicine decreases leukocyte chemotaxis and phagocytosis and inhibits the formation and release of a chemotactic glycoprotein that is produced during phagocytosis of urate crystals. 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. Colchicine has no analgesic or antihyperuricemic activity. Colchicine inhibits microtubule assembly in various cells, including leukocytes, probably by binding to and interfering with polymerization of the microtubule subunit tubulin. Although some studies have found that this action probably does not contribute significantly to colchicine's antigout action, a recent in vitro study has shown that it may be at least partially involved.
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Probably hepatic. Although colchicine metabolites have not been identified in humans, metabolism by mammalian hepatic microsomes has been demonstrated in vitro. Route of Elimination: In healthy volunteers (n=12) 40 - 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination. Half Life: Elimination half-life is approximately 1 hour in healthy subjects, although a study with an extended sampling time reported mean terminal elimination half-life values of approximately 9 to 10.5 hours. Other studies have reported half-life values of approximately 2 hours in patients with alcoholic cirrhosis and approximately 2.5 hours in patients with familial Mediterranean fever.
- Uses/Sources: For treatment and relief of pain in attacks of acute gouty arthritis.
- Route of Exposure: Colchicine is rapidly absorbed after oral administration, probably from the jejunum and ileum. However, the rate and extent of absorption are variable, depending on the tablet dissolution rate; variability in gastric emptying, intestinal motility, and pH at the absorption site; and the extent to which colchicine is bound to microtubules in gastrointestinal mucosal cells.
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Tubulin beta chain Cellular tumor antigen p53 Tubulin beta-1 chain Cytochrome P450 3A4 Multidrug resistance protein 1 Nuclear receptor subfamily 0 group B member 1 Proto-oncogene c-Fos ATPase family AAA domain-containing protein 5 Solute carrier family 22 member 3 Steroidogenic factor 1 |
17016423 12699389 19527023 17145705 10196521 17139284 20814887 23611293 15720245 20586571 16166440 |