406 CHEMISTRY OF THE LEUGOMAINS. 



into the body. Furthermore 3-methyl xanthin and the other two 

 di-methyl xanthins, theophyllin and theobromin, appear in the urine 

 after caffein administration and are therefore likewise cleavage prod- 

 ucts of this base. 



To Bondzynski and Gottlieb and to Albanesi is due the credit of 

 having demonstrated that caffein and theobromin were demethylated 

 within the animal body. The former worked chiefly with theobromin 

 and showed that this base was changed in dogs, rabbits and in man 

 to heteroxanthin. Kriiger and Schmidt eventually showed that in 

 addition to heteroxanthin also 3-methyl xanthin was formed. 



Albanesi on feeding caffein to dogs obtained what he first believed 

 to be heteroxanthin but which on further study by himself and 

 by Kriiger was shown to be 3-methyl xanthin. The investigations 

 of the latter are the most exhaustive. They show that when caffein 

 is given to the dog in small quantities it is excreted as 3-methyl 

 xanthin. In large doses, however, the demethylation is not so com- 

 plete and hence the several intermediate products appear. Some 

 caffein passes through unchanged. Each of the three methyl 

 groups are attacked in the organism and as a result the three di- 

 methyl xanthins, theophyllin, theobromin and paraxanthin, appear in 

 the urine. The first mentioned predominates and the other two are 

 present in about equal amounts. 3-methyl xanthin apparently is the 

 only mono-methyl derivative present. The demethylation is un- 

 questionably different in different animals as can be seen from ex- 

 periments with theobromin (p. 405), and with paraxanthin (p. 403). 

 Albanesi's statement that caffein in rabbits was changed to xanthin, 

 and in man to di-methyl xanthin (theophyllin ?) has been questioned 

 by Kriiger. While in dogs the cleavage of caffein yields chiefly 

 theophyllin and 3-methyl xanthin, it would seem that in man para- 

 xanthin and 1- and 7-methyl xanthins are the more resistant. 



It seems to be well established that caffein does not increase the 

 amount of uric acid in the urine. As shown above, however, it does 

 materially increase the amount of the purin bases. Kriiger and 

 Schmid have shown that the increase of purin bases is not propor- 

 tional to the amount of caffein administered. Thus, when only 

 0.05 g. of caffein was given 33 per cent, of its nitrogen appeared as 

 purin bases. With 0.2 g. of caffein only 19 per cent, of the nitro- 

 gen was found in this condition. The ratio of the nitrogen of uric 

 acid to that of the purin bases is 13.5 : 1 or 12.7 : 1. After caffein 

 administration it falls to 9.9 : 1 or 8.35 : 1. 



The results with theobromin were in some respects very different. 

 Like caffein it does not increase the amount of uric acid but it has 

 a greater influence upon the purin bases — the ratio being 2.6:1. 

 In other words 47 per cent, of the theobromin nitrogen appeared in 

 the form of purin bases. 



As yet there is no direct evidence going to show that xanthin is 



