14 THE TOXICITY OF CAFFEIN. 



mals except that the reflexes are almost completely lost after the sub- 

 cutaneous injection of doses of one-sixteenth to one- twelfth of a grain. 

 The latter dose was fatal for frogs. It would be of interest to know 

 the comparative toxicity of caffein to frogs and mammals, but unfor- 

 tunately the weights were not reported. 



Schmiedeberg 79 (1874) noticed that the administration of 20 mg of 

 caffein to frogs weighing about 45 grams was followed, in Rana escu- 

 lenta, in about 25 minutes, by increased reflexes, 7 minutes later 

 by tetanus. Several attacks occurred, but tonic spasms were never 

 observed. On the contrary, when the same amount of caffein was 

 given to Rana temporaria weighing 45 grams he noticed a marked 

 diminution of the reflexes and tonic rigidity of the muscles after 23 

 minutes ; the reflexes were greatly increased, however, about 24 hours 

 later. The frogs were under observation for three days, and although 

 symptoms were still present at the end of this time in the subjects of 

 both species tetanus was never observed in Rana temporaria. 



Peretti's 70 (1875) studies on the effects of caffein were confined 

 chiefly to observations on dogs. He also made observations on a 

 few rabbits and reported an experiment on one cat to which he admin- 

 istered, by subcutaneous injection, 0.18 gram of caffein per kilo and 

 noticed increased frequency in lachrymation and crying. The cat 

 was found dead the next day. The subcutaneous injection of a rabbit 

 in which artificial respiration was instituted with 0.36 gram of caffein 

 per kilo proved fatal soon after the injection without any manifesta- 

 tion of symptoms. Small doses of caffein, 0.1 gram, given to a rabbit 

 weighing 3,670 grams, failed to produce any visible effects. Doses 

 under 0.1 gram per kilo likewise failed to induce any symptoms in 

 dogs. When 0.1 gram of caffein per kilo was given by mouth or sub- 

 cutaneously it was followed by restlessness, salivation, rigidity of 

 hind legs, and vomiting. In both instances the dogs recovered. The 

 symptoms were more severe when the dose was increased to 0.185 

 gram per kilo, but even in this case the dog recovered. A dose of 0.2 

 gram per kilo, however, proved fatal. 



Henneguy 36 (1875) experimented on three frogs to which he gave 

 0.01 gram of caffein citrate subcutaneously. He observed mild stim- 

 ulation of the nervous system and of the muscles, as well as increased 

 cardiac activity. Later, voluntary movement and respiration disap- 

 peared and sensations diminished, but convulsions of the extremities 

 appeared. Cardiac activity was then diminished, the heart being 

 finally arrested in systole. Since the motor nerves retained then" irri- 

 tability even after the reflexes disappeared, he concluded that the 

 loss of motion was due to the action of caffein on the nerve centers. 



Binz n (1878) reported experiments on dogs and also made some 

 observations on man with caffein. The subcutaneous injections of 

 0.2 gram caffein may prove fatal to dogs, although some survive such 



