HISTORICAL REVII \\ . 13 



a result of caffein poisoning in mammals. Somewhat different effects 

 of caffein in frogs were observed by Buchheim and Eisenmenger u 

 ( 1870) . After the injection of 2 per cent of the citrate the frogs soon 

 become inactive. He also observed muscular twitching of the 

 extremities, which gradually increased, with rigidity of the muscles 

 and opisthotonos, while respiration became slow and superficial, 

 finally stopping altogether. 



Aubert 8 (1872) studied the toxicity of caffein hi man and other 

 animals. After the ingestion of 0.36 gram, he observed dizziness, 

 but doses of 0.12 and 0.24 gram were without any apparent effect. 

 On the other hand, a dose of 0.5 gram of caffein was followed by 

 increased frequency of the pulse, which soon disappeared. After one 

 hour he noticed dizziness and trembling of the hands, which likewise 

 passed away soon. The injection of 0.16 gram of a 2 per cent solution 

 of caffein into the jugular vein of a rabbit weighing 1,090 grams 

 caused tetanus and death in two and one-half minutes, and 0.12 gram 

 injected into a rabbit weighing 980 grams caused death in one minute. 

 Much larger doses could be borne, however, when artificial respiration 

 was resorted to. A dog which was given 3 grams of caffein survived 

 when artificial respiration was performed. Aubert reports, on the 

 other hand, a similar experiment with 0.25 gram of caffein which 

 terminated fatally. 



That caffein may give rise to different effects in various species of 

 animals was observed for the first time by Bennett. 9 He studied its 

 action on frogs, mice, rabbits, and cats, and attempted to determine 

 the minimum fatal dose in rabbits and cats. He also reported experi- 

 ments with thein. In his first communication on the subject he 

 states that the administration of thein to rabbits first increased and 

 then diminished the frequency of respiration, while the pulse was 

 decreased in frequency. Caffein, which he apparently thought was 

 different from thein, caused increased frequency of respiration, while 

 the pulse was markedly retarded after a preliminary acceleration. 

 He also noticed congestion of the ears, muscular incoordination, 

 tetanus, paralysis, diminished reflexes, and contraction of the pupils. 

 Bennett reported the minimum fatal dose of caffein for a rabbit weigh- 

 ing 3.25 pounds as being 5.25-5.5 grains. The symptoms in cats 

 after the administration of toxic doses of thein or of caffein were 

 great excitement, paralysis alternating with convulsions, and profuse 

 salivation. The minimum fatal dose for a cat weighing 5 pounds 

 was, according to Bennett, 6 grains of caffein and 5.5 grains of them. 

 Only one experiment on a mouse is reported; the administration of 

 0.1 grain proved fatal. The symptoms were the same as those 

 observed in cats and rabbits after the administration of caffein. The 

 experiments on frogs indicate that the symptoms were about the 

 same as those previously described in the case of warm-blooded ani- 



