190 Colchicine 



pected to exist. l)ui tlic lollowino results are not necessarih the con- 

 sequence ot mitotic poisoning. 



In hens, 1.5 nig/kg of colchicine causes death in 36 to 48 hours. 

 The symptoms are those already described: diarrhea, vasomotor dis- 

 tmbances, and nervous paralysis. Injections of 1.2 mg/kg are not fatal. 

 They cause a shedding of the feather buds in j^laces where the feathers 

 were remo\ed 15 days previously.- The feathers which grow next have 

 a white extiemity. Two similar injections, 7 and 14 days later, give 

 to these feathers a deejj black barring. The other feathers of the 

 animals darken. An analysis of the rate of growth of the feathers 

 demonstrates that colchicine acts immediately and that it modifies the 

 feather gro^\•th for 4(S hours. It was demonstrated lateri'^ that the 

 section of the spinal ner\es could bring about similar changes of color. 

 The authors are led to the conclusion that colchicine may act b\ affect- 

 ing the nerxous sxstem. a conclusion remarkably in line with later 

 research.--^ 



7.5: Nonspecific Toxic Changes 



In considering the modifications of an organism \vhich lias been 

 injected or which has received by any route a substance as toxic as 

 colchicine, nonspecific changes must be taken into account.'''' These 

 may be difficult to sejjarate from effects of the drug itself, and only 

 future work will enable this aspect of the subject to become clearer. 

 For instance, while the influence of the pituitary-adrenal sxstem is 

 known to be great in all types of "stress," there are only txvc^ jjapers 

 on the action of colchicine in adrenalectomized animals. -^^- It was 

 demonstrated that an important ninnl)er of the nuclear pycnoses of 

 thymus and lymphoid tissue are only indirectly the consecjuencc of 

 mitotic jjoisoning. Pycnosis is much less ajij^arent in adrenalectomized 

 animals. ^- Xo work has been reported on the general effects of the 

 alkaloid after hypophysectomy. This should be important, consider- 

 ing the possibility of the jiituitary gland taking part in some central 

 nerxous stimulation of leukocytosis. 



The facts assembled here may only have a distant relation to stress 

 and the alarm-reaction. It is known, howexer, from experimental 

 work-^* and from human pathology-"' that this reaction can appear 

 after colchicine. Also, sexeral of the changes reported have also been 

 obserxed after other mitotic poisons, chemicallx unrelated to col- 

 chicine. ■•"■ It is logical to believe that they belong to the vast groiij) ol 

 nonspecific tissue changes."'* 



7.5-/.- The "Jionnonr-mhnetic" actions of colchicine. The idea 

 of colchicine haxing some direct hormonal action xvas put lorxvard b) 

 botanical work."'- It led to some curious experiments which are im- 



