OAFFEIN. 405 



Obviously theobromin may be expected under like conditions in 

 human urine. 



The base has been synthesized by Fischer* out of 1-3-di-methyl 

 uric acid ; also from uric acid itself by converting this into 3-methyl 

 uric acid. Traube^ likewise prepared theobromin by treating 3- 

 methyl xanthin with methyl iodid. Theobromin can be readily 

 methylated to caffein. 



The changes which theobromin undergoes in the body have been the 

 subject of a number of very interesting investigations. Bondzynski 

 and Gottlieb' in 1895 showed that it underwent cleavage when 

 fed to rabbit and to dogs. In rabbits only 19 per cent, of the 

 theobromin was recovered unchanged, and 24.6 per cent, was ob- 

 tained as a methyl xanthin which these workers identified with 

 heteroxanthin, although as pointed out on p. 398 this substance 

 must have been mixed with some 3-methyl xanthin. Xanthin 

 itself was not obtained. Similar though incomplete experiments 

 with caffein seemed to give the same methyl xanthin. They also 

 found that when theobromin was administered to a leukemic that it 

 was excreted as such and as methyl xanthin in about the same 

 amounts as in a healthy person. According to Rost's* experiments 

 the dog will excrete about 31.8 per cent, of the administered theo- 

 bromin ; the rabbit 28 per cent, and man 20 per cent. Unlike 

 caffein, the base produces diuresis in the dog and hence the much 

 greater elimination of theobromin (page 345). 



About the same time Albanesi experimented with caffein and like- 

 wise obtained a methyl xanthin which was assumed to be hetero- 

 xanthin, but was eventually shown to be 3-methyl xanthin (p. 395). 

 Kriiger and Schmidt fed theobromin to dogs and found that they 

 eliminated some unchanged base, chiefly 3-methyl xanthin and some 

 7-methyl xanthin or heteroxanthin. In rabbits the results were quali- 

 tatively alike, but differed quantitatively. In addition to theobromin 

 their urine contained chiefly 7-methyl xanthin and but little 3-methyl 

 xanthin. Later Kriiger showed that caffein splits up in the dog into 

 theobromin and other cleavage products (p. 406).) 



Caffein or 1.3.7-tri-methyl xanthin (p. 340), C^^^p^, is the 

 active principle of tea and coffee and while it is not a product of 

 tissue metabolism in the animal body it is of interest because of its 

 relation to xanthin and its derivatives as well as to uric acid. Of the 

 ordinary purin bases found in human urine only adenin, hypoxan^ 

 thin and xanthin are cleavage products of the nucleins of the tis- 

 sues. 1- and 7-methyl xanthins (heteroxanthin) and 1-7-di-methyl 

 xanthin (paraxanthin) are undeniably derived from the caffein taken 



' BeriohU, 30, 1839 ; 31, 1980 ; 32, 470. 



'Berichte, 33, 3050. 



^Arehiv. Path. u. Pharm., 36, 45, 133 ; 37, 385 ; BerichU, 28, 1113. 



' Arehiv. Path. u. Pharm., 36, 56. 



