Pharmacology 179 



colchicine was called "this most remarkable sUnv i)()ison."-" Progres- 

 sive nervous paralvsis leading to respiration arrest, appears to be the 

 main cause of death, whatever the animal tested. Recent research has 

 brought new emphasis on this nervous action ol colchicine.--' 



y.^^-i: Nerx'ous system, central and JMni j^lioal. An experiment 

 jjerlormed nearh' 50 years ago gives a remarkable demonstration ot 

 the sensitivitv ot the nervous system towards colchicine. While the in- 

 jection ot even the largest doses killed a cat only alter several hours, 

 the intracerebral injection ot the drug had a spectacular and rapid 

 action. Very soon the blood pressure was found to increase, and the 

 respiration became rapid and deeper. After 35 minutes, a sharj) fall in 

 the blood pressure indicated vasomotor paralysis. One hour alter the 

 injection, the animal died of respiratory paralysis.-" 



.\n important series of findings in rats and cats points to the 

 ner\()us s\stem as one of the principal causes of the various etlects of 

 colchicine poisoning. This work can only be summarized here. 2=^ 

 Some of the most significant obser\ations are listed. Vomiting cannot 

 be, as was sometimes thought, the consequence of pathological modi- 

 fications of the gastrointestinal tract brought about by mitotic arrest. 

 The same is true for diarrhea, a frequent synijitom, which would 

 appear to be a consequence of intestinal congestion and ulcerations. -« 

 No diarrhea and almost no vomiting is found in animals injected with 

 barbiturates, even when the dose of colchicine is lethal. 



The central temperature falls sharply after colchicine. This may 

 be pardy a result of stress and nonspecific toxicity'^ «•• (Fig. 7.2) . but 

 the cur\es indicate that the decrease taking place in the first ten hours 

 has another cause. This is now believed to be a central nervous effect.--^ 



Another fact points in the same direction: Animals treated with 

 colchicine display an increased sensitivity. While unanesthetized cats 

 die only after eight to ten hours, the same dose of colchicine brought 

 death in less than two hours when the animals had received barbi- 

 turates jM'eA-iously.--^ Barl)iturate or ether anesthesia also proved to 

 be abnormally dangerous in animals which had received the alkaloid 

 first. 



Arterial constriction leading to high blood pressure has been men- 

 tioned. Experiments of brain transsection in the cat demonstrated thai 

 this also was a consccjuence of a central nervous stimulation.-"- 



Howe\er. other territories of the ner\ous system are attectcd In 

 colchicine. The neuromuscular apparatus appears to be the most 

 sensitive, though only after repeated administration of the alkaloid 

 can the modifications be detected. An atrophy of the hind (piarters 

 of cats injected daily with 0.05 mg. per kg. of body weight was ()l)ser\ed 

 after two weeks. The leg muscles were converted into thin strands. 

 There was no e\idence of muscular damage. .Abnormal responses U) 



