Colchicine and its analogs in gout: A brief review

Abstract

REVIEW of our knowledge of colchicine as it pertains to its effects A in relieving the symptoms of acute gout is useful for at least two reasons.One is that further study of the disorganizing effects of colchicine on the mitotic spindle, probably composed of a fibrous protein with a sulfhydryl riidical, may lead us to the identification of a possible intermediary sulxtance in purine synthesis responsible for the acute gouty attack. Secondly, with the availability of many new colchicine analdgs, there is hope that a more eitective, less toxic. anti-gout drug than colchicine may be discovered.The literature' pretaining to colchicum, the crude extract. and colchicine, one of its purified extracted ingredients, is extremely voluminous, in spite of the fact that comprehensive research in this field begm as late as 1934, with the observation by A. P. D~istiii, Sr.2 that colchicine had B unique effect on mitosis, poisoning the spindle at the metaphase of cell division. We now know that as little as one part in a billion can produce this effect.Mitotic poisons had been studied for a long time, iictually since Hertwig ( 1887),3 who worked with narcotics. A. P. Dustin, Sr. had experimented with many chemicals before his attention was directed to colchicine. Since 1934, colchicine has been used to an enormous extent in such diverse fields as agriculture, genetics, cell physiology, the study of birth malformations and cancer research. Before its demonstration as a mitotic poison, its only usefulness was in the treatment of gout, based on empirical observation dating hack to the (lawn of history. Those interested in the absorbing historv of colchicum may read the author's paper." THE NATURALLY OCC;URRING COMPOUNDSAlthough the exact formula of colchicine, one of the purified ingredients of colchicum, is now well established, its actual synthesis in the laboratory has not been accomplished. We still must obtain our materials from the natural source. There are 64 varieties of the plant colchicum (B. Stefanoff, 1928),6 all members of the lily family. At least 30 cwntain colchicum. In the western world, the source is mainly the corm m d seed of Colclzicunr crzrtunrrde, a plant found growing wild in the hlediterranean basin. Many other varieties are found further west, to the foothills ok the Himalaya Mounatins.Briefly, colchicine is extracted from the corm and seed with alcohol and water, and then from this solution with chloroform. The latter is evaporated off, yielding amorphous colchicine, which can be crystallized from solution in ethyl acetate. Chromatographic purification is then accomplished by the method of Ashley and Harris (1944).'; This yields practically pure colchicine. Santavy and his co-workers have extracted iit lwst nine other analogs naturally present in the plant itself. From these basic natural compounds a host of syntheticallv derived analogs have been developed, mainly for experimental 18

Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims

“…Colchicine, originally derived from the plant Colchicum , had its medicinal value recognised several thousand years ago and has been used for gout for at least several hundred years 8. It downregulates inflammation through blocking microtubule spindle formation, disrupting inflammasome function, inhibiting cytokine production and hindering neutrophil chemotaxis 9.…”

Contentious Issues in Gout Management: The Story so Far

“…Colchicine has been used in the treatment of gout for centuries. 69 It blocks microtubule spindle formation, which leads to decreased cytokine production, downregulating neutrophil chemotaxis, and hinders the inflammasome function.…”

Poisson poisoning as the mechanism of action of the microtubule-targeting agent colchicine

“…Colchicine, extracted from Colchicum autumnale (1), is a drug first discovered to relieve symptoms of gout based on experimental observations in 15 th century (2). In the early 1930s, several studies showed that colchicine had a unique effect on mitosis, arresting cell division at metaphase in tissues both in vivo and ex vivo, without knowing its primary binding target in cells (3)(4)(5)(6)(7).…”