HKVIKW. 9 



HISTORICAL REVIEW OF THE LITERATURE ON THE TOXICITY 



OF CAFFEIN. 



Caffein was discovered in 1820 by Runge, 77 Pelletier, 89 and Robi- 

 quet 76 and was first analyzed by Dumas and Pelletier, 20 but its 

 exact percentage composition was determined by Pfaff and Liebig, 

 71, 72 w hil e to Herzog 13f 83 belongs the credit of having established 

 that it is basic. Strecker 82 prepared caffein synthetically by heating 

 theobromin silver and methyl iodid in a closed tube for 24 hours. 

 Soon after its discovery in coffee Oudry 67 reported the presence of 

 a substance in tea which he called "thein." Its identity with caffein 

 was established 15 years later by Jobst 43 and also by Mulder. 62 ' M 

 According to Brill, 13 Mulder (1838) was also the first to perform 

 experiments with caffein on animals. After the administration of 

 one-half grain to a pregnant rabbit he observed loss of appetite and 

 kyphosis. The rabbit aborted but recovered from the effects of 

 caffein. It has since been made the subject of numerous investiga- 

 tions which were carried out on a variety of animals. Observations 

 with caffein were also made on the human subject. About four 

 years after Mulder published his results, Lehmann 61 (1842) reported 

 experiments on a number of people who were given caffein. The 

 administration of from 2 to 10 grains of the alkaloid was followed by 

 headache, palpitation of the heart, increased frequency and irregu- 

 larity of the pulse, tinnitus aurium, photopsia, insomnia, and even 

 delirium. Similar experiments reported by Frerichs 2S (1846) indi- 

 cate that in doses of 25 grains it may induce severe symptoms about 

 15 minutes after its administration. He also observed circulatory as 

 well as nervous symptoms and vomiting. 



According to Albers 2 (1852), 4.5 grains of caffein citrate injected 

 subcutaneously into the thigh of a rabbit was soon followed by dimin- 

 ished motion and tremors of the operated thigh. Other symptoms 

 reported were spasms of the facial muscles, increased respiratory 

 movements, and mental confusion. Of interest in this connection 

 are the experiments of Cogswell 17 (1852) on frogs. He concluded that 

 in point of destructive action on the tissues, caffein is far superior 

 to morphin and may be compared to strychnin and coniin, its action 

 on the nervous system he believed to be principally confined to the 

 effect on the brain and spinal cord. 



Lehmann 52 (1853) observed increased frequency of heart action 

 after the administration of 4 grains, which were given with a normal 

 diet to an adult man. When the dose was doubled the frequency of 

 the pulse was still more increased, heart action became stronger, and 

 tremors and confusion of thought with excitement of the imagination 

 made their appearance. There was also an increased desire to 

 micturate. 



