Pharmacology 181 



e\u cinch toxic in I'rogs.^^ II the injected animals leapt within a few 

 minutes after tlic cliuo- took effect, their legs remained stretched and 

 exhibited fibriliarx twitchings. The rectus abdominis muscle of the 

 frog was also modified by colchicine, and contracture appeared after 

 repeated stimulation. ^'^ This was considered to be a "i.undsgaard 

 effect," identical whh thai induced by many sul)stances iniei lering with 

 glycolysis. 



A detailed analysis of the sartorius muscle of frog treated with 

 especially purified preparations of colchicine has brought to light many 

 facts, which will be summarized here and which are illustrated by 

 Figure 7.3. The curarized muscle preparation was subjected to supra- 

 maximum electrical stimulation. Colchicine concentrations above 10"^ 

 M produced a sustained increase in contractile force, which reached 

 more than 60 per cent with 1.6 X 1^^ " '^^- Larger doses resulted in 

 contracture and failure to respond to stinuilation. The increased con- 

 tractility was paralleled by an increased demand for oxygen, which 

 may be the double of the controls after two hours. Cafieine ajjpeared 

 to act synergically on this increase in oxidative processes, while meta- 

 bolic inhibitors such as azide, fluoroacetate, and malonate jMevented 

 this action of colchicine. The rate of glycolysis was increased two to 

 three times with colchicine concentrations of 6.4 X 1*^ " ^^^' ^s evi- 

 denced by the amount of lactate produced. Hydrolyzable, but not in- 

 organic, phosphorus was also increased. These facts do not ajjpear 

 to point towards a change in ATP utilization. They resemble closelv 

 those of caflfeine. The action of colchicine in increasing the available 

 energy is called "relative rarity," and thus one more curiotis effect of 

 the alkaloid appears to have been discovered. 2=* 



7.5-5.- Smooth inii.scic (Did intestine. Conflicting re}>()its have 

 been puljlished on this subject. Ihe discovery tliai diarrhea is of cen- 

 tral origin may be the explanation. A strong increase in the intestinal 

 movements has been described in animals under ether anesthesia. •'■' 

 A similar effect has been found in frogs.-*' It was abolished by atropin. 

 Increased tonus and atitomatic movements have also been described 

 in sj)leen, uterus, and bronchioli. In the dog, the action on smooth 

 muscle has been said to l)e innnediate, resembling that of pilocarpin, 

 and to be antagonized by atropin.-' Quite different results have been 

 reached by other workers on isolated intestine.-'' ^^ The innnediate 

 effect was one of depression. The reactions towards adrenalin and 

 atropin were not altered. 



The local action on the intestine is paralytic, and was found to be 

 related to the changes taking place in the mucosa, especially hemor- 

 rhage.-*^ In a cat, injections of colchicine (1 mg. in saline) were made 

 in liuated seements of the small intestine. A strong congestion and 

 hemorrhages arc to be seen locallv within 21 hours. With larger doses. 



