568 Mr. V. H. Veley and Dr. A. D. Waller. [June 17, 



and there results an increase in the free cholesterol of the blood. Phytosterol 

 does not appear in the blood as such. 



We take this opportunity of expressing our thanks to the Government 

 Grant Committee of the Eoyal Society for assistance in carrying out this 

 work. 



On the Comparative Toxicity of Theobromine and Caffeine, a& 

 Measured by their Direct Effect upon the Contractility of 

 Isolated Muscle. 



By V, H. Veley, F.E.S., and A. D. Waller, M.D., F.K.S. 

 (Eeceived June 17,— Read June 30, 1910.) 



Introductory. 



The isolation of caffeine from coffee is generally assigned to Eobiquet, 

 Pelletier and Caventou (1821),* though the so-called coffee base, obtained a 

 year previously by Eungef was probably impure caffeine. 



The identity of theine, extracted from tea by Oudey (1838),j with caffeine 

 was established by the analyses of Jobst (1843).§ The association of caffeine 

 with uric acid was noted originally by Stenhouse,|| who found the latter in a 

 sample of Paraguay tea. 



Theobromine was first isolated by WoskrcsenskylF from cocoa (1842), and 

 its association with alloxan, on the one hand, and caffeine on the other, was 

 established by subsequent observers. 



According to the investigations of Emil Fischer (1894 — 1898),** uric acid, 

 theobromine, caffeine, and other allied substances, are derived from the parent 

 base purine, to which the following, as one of two alternative forniute, was 

 eventually assigned : — 



N 1 



lie 



HC N 



/ 6\y V,\cH 



2 4 



N 



NH 



* 'BerzeliuH Jahrcsljer.,' vol. 4, j). 180, and vol. 7, p. 269. 

 + ' I'liytoclu'iiiisclicr Entdeckungeii,' p. 144, Berlin, 1820. 



I 'Mag. riiarin.,' vol. V,), p. 49. 



§ ' Annalen,' 18.38, vol. 35, p. 63. • 



II find., 1843, vol. 46, p. 371, and vol. 46, p. 227. 

 If Ihid, 1842, vol. 41, p. 126. 



** ' UnterBuchungen in dcT I'lirin-Gruppe.' Collected volume, Berlin, 1907. 



