6 THE TOXICITY OF CAFFEIN. 



interest in this connection. He made the important discovery that 

 some animals possess the power of methylation as well as of demethyl- 

 ation. Abderhalden and Brahm's l experiments with pyridin show 

 that the same is true of young dogs when on a meat diet. His experi- 

 ments on rabbits with this substance were negative. 



The metabolism of caffein and theobromin furnish another illustra- 

 tion of differences in the physiological mechanism of animals. Al- 

 though the substances found in the urine of man, dog, and rabbit after 

 the administration of caffein and theobromin were the same, the quan- 

 tities varied considerably. According to Kriiger and Schmidt, 47 over 

 14 per cent of the theobromin introduced into the rabbit is eliminated 

 as 7-methyl xanthin in the urine. The dog eliminates only about 0.67 

 per cent. On the other hand, the amount of tri-methyl xanthin elimi- 

 nated was only 3 per cent in the dog and not quite 1 per cent in the 

 rabbit. 



It appears, therefore, from studies in comparative metabolism, 

 whether endogenous or exogenous, that well-marked physiologic and 

 chemical differences exist in various species of animals. That phar- 

 macological action may likewise vary in different species of animals 

 is shown by the following investigations. According to Gurnard, 31 

 who made an exhaustive study of morphin, the reaction to this alka- 

 loid varies in different forms of life, both qualitatively and quanti- 

 tatively. He established its narcotic effect in the dog, rabbit, guinea 

 pig, white mice, and rats, while for the cat, horse, ox, sheep, hog, and 

 goat it is, on the contrary, a stimulant. Moreover, there is no evi- 

 dence of cerebral effect. --The stimulating effect of morphin on the 

 nervous system in some animals was also observed by Noe 65 in experi- 

 ments with this substance on the hedgehog. 



Guinard 29> 30 has also shown that morphin has no narcotic effect in 

 the marmot, although this animal is very sensitive to the drug. Two 

 milligrams per kilo were found to be a surely fatal dose for this animal. 

 His experiments on the comparative toxicity of morphin 30 31 show a 

 considerable range of variation in different species. Thus the fatal 

 dose for the dog was found to be 0.65 per kilo, while 7 mg per kilo is 

 the fatal dose for the horse. About twice the amount is fatal for the 

 ox and 0.2 mg per kilo kills the pig. Experiments with other drugs has 

 shown that a considerable range of variation in resistance exists in 

 animals of different species. 



Noe's 65 studies on the comparative toxicity of chloral brought out 

 the interesting fact that the rabbit is more resistant to it than the 

 hedgehog and the latter more resistant than the guinea pig. Per- 

 haps the most striking example of a difference in reaction of the 

 same substance in widely different species is that furnished by 

 apocodein, quinin, and yohimbin. According to Gunn 32 these sub- 



