Pharmacology 195 



about I he same in mammals and frogs when the latter are kept at 

 30-32 °C. 



It was also known that solutions of colchicine that had l)een left 

 standing- and haAC become brownish, probably as a result of oxidation, 

 become far more toxic to frogs, even at low temperatures.-^-^ In 1890, an 

 attempt was made to separate the toxic fraction of these oxidized 



TABLE 7.2 



Relative Toxicity of Colchicine 



(After Fuehner^*) 



Lethal Doses. After 

 Subcutaneous Injection 



Species (gm /kg of body weight) 



Rana esculenta, 15-20°C L200-2.000 



Rana esculenta, 30-32=0 . 002-0 . 004 



White mouse 0.003-0.010 



Rabbit 0.003-0.005 



Dog 0.001 



Cat 0.0005-0.001 



preparations, and a substance tentatively named "oxydicolchicine" 

 ^\•as isolated. 1 his was believed to be made of iwo molecules of col- 

 chicine linked by an oxygen atom.^^ Artificial oxidation of colchicine 

 with ozone yielded a similar substance. A ftnther experiment at- 

 tempted to prove that the kidney was the organ in which colchicine 

 was oxidized to a more toxic product. About 330 mg. of amorphous 

 colchicine -were added to defibrinized hog's blood, and this was slowly 

 perfused through the hog's kidney. From this organ 42 mg. of a 

 brown substance were recovered. This, like "oxydicolchicine," dis- 

 played a rapid toxic action in the frog, where the symptoms were vis- 

 ible about one hoin- after the injection of 30 mg. 



These experiments do not appear to ha\e been checked by modern 

 methods. This would be interesting now that the chemistry of the 

 alkaloid has made such great progress (cf. Chapter 6) . No std^stance 

 of the structure assigned to '"oxydicolchicine" has been described. On 

 the other hand, experiments ^viih mitotic poisoning are conflicting. 

 In mice, solutions of colchicine lose about 20 per cent of their cytologi- 

 cal activity after fi\e weeks of standing.^" 



The fate of colchicine in the animal b(Kly has been si tidied by 

 modern methods, chemical, biological, and physical. A colorimetric 



