196 Colchicine 



method ol titration was checked by measuring the mitosis-arresting 

 properties ot solutions either by injecting them in mice or by study- 

 ing their action on tissue cultures. ^^ Alter a single injection the blood 

 level in the adult rat decreased rapidh, and remained stable alter 

 a few minutes. The tissues contained less alkaloid than the blood. 

 Elimination was by the bile and intestine, and within a few hours, 

 10 to 25 per cent of the dose injected was to be loimd in the intestine 

 and its contents. Elimination by the urine only lasted a short time, 

 wdiile the blood concentration was at its highest. Within If) hours, 

 50 per cent appeared to have been eliminated. There was neither 

 evidence of a change into a more toxic substance, nor of any selective 

 tissular fixation. The cumulative toxicity of repeated injections is a 

 simple consequence of the slow excretion. 



By growing Colchicujn in an atmosphere containing radioactive 

 carbon, C'^, in the form of CO,, a biolooical svnthesis of radio- 



— o / 



active colchicine has been made possible.'^*' lire fate of this in 

 the body of mice has been tested. One fact of imjjortance is that four 

 hours after the injection, no more colchicine coidd be detected in the 

 central nervous system, muscle, heart, or blood. Most of the radio- 

 acti\e alkaloid ^vas detected in the kidney, the sjjleen, and the intestine. 

 Neoplastic tissue (sarcoma 180) did not contain more colchicine than 

 the liver. An unexplained fact is that while the spleens of control 

 animals were a site of active fixation, no more colchicine could be 

 found in this location in tumor-bearing mice.^ These observations 

 appear to demonstrate that the alkaloid brings about quite rapidly 

 some change in the brain without becoming fixed in this tissue.^ 

 Evidence will be presented elsewhere (Cliapter 9) that colchicine may 

 be retained for some time in tissues of cold-blooded animals {Xenopus 

 tadpoles) . 



Finthei" research is also necessary in this field, for there appears 

 to be some contradiction between the stability of colchicine as evi- 

 denced from old and modern work, and the l)iological activity and 

 specificity of this molecule. These problems will be discussed in the last 

 chapter of this book. 



7.7: The Treatment of Gout 



Logically, colchicine pharmacology should be an introduction to 

 its use in medicine and should enable us to imderstand why this 

 plant alkaloid is elfective in treating a disease of inic-acid metabolism. 

 However, as will be noticed, actual data on ]jharmacology are of 

 small helj) in understanding the curative properties of Colchicum. 

 Many complicated side-effects have been described, many strange 

 properties investigated, but modern medicine is ajjparently not much 

 closer th:in the Ebers Papyrus in explaining the medical use of this 

 plant. 



