14 Colchicine 



During the latter eighteenth and beginning nineteenth centmies, 

 many English and French physicians wrote extensively about gout, 

 recommending Cohliic iini lor reliel. The great nineteenth century 

 doctor, Thomas Sydenham, who styled himself as the English Hippoc- 

 rates,^-' was a martyr to gout. He offered theories tor its natine and 

 cause, and advocated treatment with Colcliiciu)}. Another successful 

 student and physician was Alfred Baring Garrod, whose books^'-^* and 

 papers contained \aluable data about the changes indticed by gout. 

 In the nineteenth centiuy almost every prominent doctor with a 

 knowledge of gotit had a j^artictdar theory as to its origin and natme. 

 The forty-seven cases studied by Garrod are classic examples of soiuid 

 scientific investigation. Like others, he stood behind the Colchicum 

 treatment even though the poisonous nattue of this crtide drug was 

 well known. 



An application of (olchicine reported in modern medical prac- 

 tice is the treatment of Hodgkin's disease in which instance remis- 

 sions were obtained.-' 



1.4: Chemical Studies of the Pure Substance Colchicins 



Accuracy in treating gout and in j^erforming critical experiments 

 demanded j)ure substances. Until the chemists' analysis and ex- 

 traction of crystalline compounds from corm and seed, only the crude 

 material was axailable to provide the active )jrincij)les in the drug. 

 A toxic principle invoh ing ptue colchicine was detected in substance 

 from Colchicum seed in 1(S2(),-^- but the compoiuid was confused with 

 veratrine. Later the name colchlciuc'^^' was jjroposed for a crystalline 

 material extracted by chemical procedures developed for this pin jiose. 

 Thus, the first steps were taken toward solving the problems in the 

 chemistry of colchicine. C^hapter 6, devoted to the chemistry of this 

 substance, illustrates the exceedingly complicated analytical work 

 necessary to tmderstand colchicine chemistry, much less to contribute 

 to its development, liut the rewards in a broad field of biology appear 

 promising for experimenters who can obtain derivatives of known 

 chemical organi/atif)n and apjjly the same to critical biological test 

 cjrganisms. 



Thorcjugh descriptions characleii/ing crystalline colchicine were 

 prepared by Zeisel in 1883, and by Houdc- in 1884.^ The formula 

 G22H2,;0,;N was proposed. •^■'^ These analytical developments formed 

 the groundwork for later work. Pharmacological studies using colchi- 

 cine and its derivatives coidd then jjroceed on a sounder basis, as 

 shown by the work done dining the next several decades from the 

 laboratories of Jacobj and Fuhner.^ 



One of the first derivatives studied was colchiceine, obviously 

 demonstrating different biologicaH- activity from that of colchicine. 



