1910.] Comparative Toxicity of Theobromine and Caffeine. 569 



The figures denote the relative positions of the substituting groups proposed 

 originally by Fischer, and now adopted in chemical literature. 



Theobromine is 3.7-dimethyl-2.6-dioxypurine, and caffeine or theine is 

 1.3.7-trimethyl-2.6-dioxypurine : — 



OC NCH3 



C ' 



N 



OC 



NCH3 



Theobromine. 



CH 



NH 



OC NCH 

 / \/ \CH 



OC 



NCH3 



Caffeine. 



NH 



Hypoxanthine is monoxypurine and guanine its mono-amino derivative, 

 xanthine is dioxypurine and uric acid is trioxypurine. 



Unfortunately, the bases guanine and xanthine, as also uric acid, are too 

 insoluble in water (less than 1 part in 1000) for the purpose of our 

 investigation. Among coffee extractives is caffeo-tannic acid, C15H18O2, which 

 occurs as a magnesium or calcium salt in the berries (Eochleder)* ; it is a 

 gummy substance readily soluble in water and alcohol. 



The substances investigated are theobromine, caffeine, caffeo-tannic acid, 

 and an artificial mixture of caffeine and tannic acid, as also extracts of tea 

 and coffee (with or without caffeine). 



Caffeine ( Trimethyldioxypurine). 



All the records obtained were similar in type, the muscle going into 

 contracture, and abolition finally taking place in a longer or shorter time 

 according to the concentration. 



In the record given (fig. 1), which is quite characteristic, a n/200 solution 

 of caffeine (O'l per cent.) produced abolition in 11"5 minutes ; in other 

 experiments on other days with solutions of the same concentration the times 

 were lO'o and 11 minutes respectively, and in a fourth experiment on a 

 cooler day, and consequently at a lower temperature (which, however, we 

 omitted to note), the time was 14 minutes. With a solution of double the 

 concentration, namely, n/100 (0*2 per cent.), abolition took place in 

 4 minutes. 



In earlier experiments with caffeine hydrochloride and hydrobromide 

 solutions (?i/200 concentration) contracture took place immediately; this 

 more rapid effect is attributable to the conjoint action of the caffeine and the 



* ' Annalen,' vol. 59, p. 300. 



