HISTORICAL REVIEW. 11 



spinal cord, and brain, sensation being paralyzed before movement. 

 The injurious action of caffein proceeds, according to Hoppe, from 

 the spinal cord. This was based on experiments on two frogs, Rana 

 esculenta, in which the right leg was amputated, the nerve being left 

 hit act, while the nerve of the other leg was ligated. At the end of 

 30 minutes paralysis was more marked on the right than on the left 

 side. In another frog of the same species he resected the femoral 

 nerva on the right side; about 1 hours after the administration of 

 caffein convulsions were observed. The left leg was rigid, but the 

 right was relaxed. 



Voit 85 (1860) ligated the vessels of the right lower extremity, cut 

 the nerves of the left leg, and introduced a few drops of caffein 

 solution into the stomach. Shortly afterwards tetanus of the right 

 leg occurred on touching the back of the animal; the left leg was 

 motionless. Later the entire body exhibited tetanic convulsions. 

 From this and similar experiments Voit concluded that caffein acts 

 first and principally on the central nervous system, and that caffein 

 is also poisonous to nerve and muscle libers, as they die when a solution 

 of caffein is applied to them. The action of caffein, according to 

 Voit, is similar in great part to that of strychnin. The effect on the 

 blood vessels is particularly interesting, as Voit observed dilatation 

 of the vessels, due as he thought to muscular paralysis, and also trans- 

 udation and congestion of the capillaries. 



Kurzak 48 (1860) made a study of the comparative toxicity of 

 caffein in frogs and rabbits and came to the conclusion that the lethal 

 dose for frogs is about one-seventh of that for rabbits. Caffein 

 citrate in the form of crystals was administered in both cases by 

 mouth. The doses given to frogs were 1 to 1.5 grains. He observed 

 convulsions and increased respiratory activity at first; after one hour 

 respiration diminished and voluntary muscular activity disappeared. 

 Even on the second day convulsions were sometimes noticed. Death 

 occurred at the end of the first or second day. Experiments on 

 only two rabbits were reported, 0.8 gram of caffein citrate causing 

 the death of one at the end of 13 hours. The symptoms noticed were 

 the same practically as in frogs, but it is interesting to observe that 

 ecchymosis of the mucous membranes of the stomach near the cardia 

 was the only lesion found on autopsy. Several experiments made 

 on different days on the other rabbit indicated that the toxic 

 dose exceeded 0.5 gram, while smaller doses caused but very mild 

 symptoms. 



According to Gentilhomme ** ( 1867) , after caffein the reflexes are at 



first diminished and then disappear altogether. Death is produced 



1 by stiffness and immobility of all the muscles, particularly of the 



muscles of respiration, thus causing asphyxia. He furthermore held 



that caffein has no effect on cardiac or smooth muscle fiber, its action 



