BASES DERIVED FROM THE PROTEINS 233 



the most active of the many similarly constituted derivatives 

 which are conceivable. Some of these derivatives have 

 formed the subject of papers by Loewi and Meyer {Arch, 

 exp. Path. Pharm. 1905, 53, 213) and by Dakin (Proc, Roy. Soc. 

 B, 1905, 76, 491) dealing only with bases closely related to 

 adrenaline; more recently a much larger number of bases, 

 differing more widely in constitution, have been dealt with by 

 Barger and Dale (Journ. Physiol. 1910, 41, 19). Some of the 

 conclusions arrived at in their paper are as follows : 



(1) An action simulating that of the true sympathetic 

 nervous system is not peculiar to adrenaline but is possessed 

 by a large series of amines, the simplest being primary fatty 

 amines. Such amines are called " sympathomimetic." 



(2) Approximation to adrenaline in structure, on the whole, 

 is attended with increasing intensity of sympathomimetic 

 activity and with increasing specificity of the action. 



(3) All the substances producing the action in characteristic 

 manner are primary and secondary amines. The quaternary 

 amines corresponding to the benzenoid members of the series 

 have an action closely similar to that of nicotine. 



(4) The most suitable carbon skeleton for sympathomimetic 

 activity consists of a benzene ring with a side chain of two 

 carbon atoms the terminal atom in which bears the amino- 

 group. Another preferential condition is the presence of two 

 phenolic hydroxyls in the 3 14 position relatively to the side 

 chain ; when these are present, an alcoholic hydroxyl still 

 further intensifies the activity. A phenolic hydroxyl in the 

 2 position does not increase activity. 



It is perhaps worth while to illustrate these conclusions by a 

 few examples. yS-Phenylethylamine, C 6 H 6 . CH 2 . CH 2 . NH 2 , one 

 of the bases formed as a product of putrefaction, which has the 

 same carbon skeleton as adrenaline, is five or ten times more 

 active in raising the blood-pressure than the most active fatty 

 amine, thus illustrating the importance of the phenyl group. 

 The introduction of a methyl group or of an alcoholic hydroxyl 

 or of both, which increases the resemblance to adrenaline in 

 structure, as in the base C C H 6 . CHOH . CH 2 . NH . CH 3 , does 

 not enhance the physiological activity. More active bases can 

 only be obtained by the introduction of phenolic hydroxyls ; a 

 single one of these, in the para position, is already very effective. 

 Again, however, the activity of ^-hydroxyphenylethylamine 



