16 THE TOXICITY OF CAFFEIN. 



strychnin poisoning. Parisot found, however, that muscular rigidity 

 developed, although very gradually, also in the green frog, but it set 

 in much later than in frogs of the other species and without super- 

 seding the clonic convulsions. According to Parisot, the muscular 

 rigidity after caffein persists after the destruction of the brain and 

 spinal cord, thus showing that it is not of nervous origin. He further 

 emphasized the difference in the behavior of these two species of frogs 

 toward caffein by stating that he never observed tetanic convulsions 

 in the red frog. His experiments also indicate that the green frog is 

 more resistant to caffein than Rana temporaria, as the same doses 

 which are fatal for the latter were only toxic for Rana esculenta. 

 The number of experiments, however, is too few to justify a positive 

 conclusion on this point. Parisot also made some experiments on 

 turtles. The results he obtained show that caffein is at least as toxic 

 for these animals as for the frogs he experimented upon, 0.33 gram 

 per kilo (carapace not included in weight) having proved fatal within 

 24 hours. Two experiments on one pigeon were also reported by the 

 same observer; two doses of 0.06 gram per kilo given at an interval 

 of four hours caused mental depression and muscular rigidity, but the 

 pigeon survived. 



Experiments with caffein on the human subject made by Parisot 

 showed that man is far more susceptible to this substance than the 

 other animals he investigated. After the ingestion of 0.3 gram of 

 caffein symptoms of intoxication pointing to cerebral disturbance 

 appeared, which became more marked when the size of the doses was 

 increased. 



It will be noticed that the nature of the action of caffein, whether it 

 is a nerve or a muscle poison, formed the subject of several investiga- 

 tions. Binz n (1890) brought forward additional evidence in support 

 of the view that caffein acts primarily on the ganglion cells, and not on 

 the muscle directly. This he has shown by injecting 0.5 gram into 

 each of two rabbits after cutting the sciatic nerve on one side ; in one 

 case he also resected the obdurator and crural nerves on the same side. 

 Clonic spasms developed in both subjects soon after caffein was given, 

 but in each rabbit the side operated upon remained paralyzed. 

 Baldi 8 (1891) studied the action of caffein on Rana esculenta. After 

 injecting from 4 to 20 mg tetanus, such as observed in strychnin 

 poisoning, was noticed. Frohner 26 (1892) made observations on the 

 comparative toxicity of caffein in domesticated animals. After the 

 administration of 5 grams of caffein sodium salicylate by mouth to a 

 dog weighing 10 kilos, he noticed salivation, restlessness, vomiting, 

 and convulsions as in strychnin poisoning. Death occurred three 

 hours after the drug was given. On autopsy he noticed mild inflamma- 

 tion of the mucous membranes of the stomach and intestines and 

 edema of the lungs ; the heart was in diastole. A dose of 2 grams of 



