2 1. lODOACETATE AND lODOACETAMIDE 



diotoxic action is mainly responsible for the death of the frogs. He also 

 observed, however, that the muscular system is affected: weakness and 

 paralysis occurred so that spontaneous movement was inhibited and the 

 animals did not right themselves when placed on their backs. Rabbits be- 

 haved very similarly following subcutaneous doses of 200-500 mg/kg and 

 it was noted that the heart became stiff in contracture soon after death.* 

 He further proved that the cardiac depression is exerted on the heart rather 

 than through the vagi by demonstrating that section of these nerves did 

 not significantly modify the effect. Dibromoacetate acted less potently and 

 tribromoacetate scarcely at all. Pohl (1888), in Prague, took up this work 

 and emphasized the action on skeletal muscle, finding in frogs and rabbits 

 that a state of rigor followed the earlier weakness, paralysis, and muscle 

 fibrillation; indeed, his frogs became so stiff they could be held out hori- 

 zontally like a stick. The first experiment, the results of which are shown 

 in the tabulation below, indicated the sequence of events following the 

 injection of 50 mg of bromoacetate into the lymph sac of a large frog. 



Time (min) Event 



1 Spontaneous movements cease 



5 Animal remains on back when so placed 



9 Muscle fibrillating and cardiac rate reduced 



15 Limbs extended stiff in contracture 



27 Cardiac standstill 



He then showed that the action is peripheral on the muscles by the follow- 

 ing experiments. Arterial ligation of one leg prevented the development of 

 rigor in the muscles of that leg at a time when rigor occurred in the normal 

 leg. A denervated muscle would not go into contracture but if stimulated, 

 either through the nerve or directly in curarized preparations, the contrac- 

 ture soon appeared, indicating that the development of rigor depends on a 

 certain degree of muscle activity. It was known that muscles in rigor are 

 often acid, but Pohl admitted that he could detect no acidity with litmus 

 paper in bromoacetate-treated muscles in rigor, an observation the signifi- 

 cance of which could not be appreciated until many years later. It is unex- 

 plained why Pohl found iodoacetate to be relatively ineffective, but pos- 

 sibly his sample of iodoacetate was defective. 



* Steinauer apparently first described the actions of bromoacetate on mammals: 

 "Die Kaninchen blinzelten mit den Augenlidern, ihre Extremitdten glitten aus, ihre 

 Schnauze sank auf die Unterlage, wdhrend sie auf Kneifen noch reagirten; die Thiere 

 ruhten mit dem Rumpfe vollstdndig auf der Unterlage." 



