i io THE SIMPLER NATURAL BASES 



The fact that the bases from a pituitary extract give the Pauly re- 

 action suggests a connection with histidine, and moreover /3-imina- 

 zolylethylamine, which is obtained from histidine by decarboxylation, 

 also causes powerful contractions of the uterus. Possibly, therefore, 

 the pituitary active principle is a polypeptide-like derivative of 

 histidine. 



Guggenheim [1913] has lately synthesised a number of bases 

 by combining amines with chloracetylchloride and treating the pro- 

 duct with ammonia. In this way, for example, glycyl-/3-iminazolyl- 

 ethylamine 



NH . CH^ 



^C . CH 2 . CH 2 . NH . CO . CH 2 . NH 2 

 CH = NX 



was prepared. The bases of this type, for which the name pep famine 

 is suggested, are therefore decarboxylated polypeptides ; their physio- 

 logical action is of the same kind as the amine from which they are 

 derived, but much weaker. 



The physiological action of pituitary extracts has been in- 

 vestigated chiefly by Schafer, in conjunction with Oliver [1895, 3], 

 Magnus [1901], Herring* [1906] and Mackenzie [1911], and further 

 by Dale [1909], von Frankl-Hochwart and Frohlich [1910], Pankow 

 [1912] and others. Pituitary extract produces a direct stimula- 

 tion of involuntary muscle, without any relation to innervation. 

 Here there is, therefore, an important difference from adrenaline which 

 stimulates sympathetic nerve endings (see p. 98). The action of 

 pituitary is most nearly allied to that of the digitalis series, but the 

 effect on the heart is slight, that on plain muscle intense. The rise 

 of blood pressure caused by pituitary is thus due to the stimulation of 

 the plain muscle of the arterioles. The rise is much smaller than in 

 the case of adrenaline and lasts much longer. A further difference is, 

 that when the blood pressure has returned to the normal, the rise 

 caused by adrenaline can at once be reproduced by a second dose, but 

 in the case of pituitary the effect of a second dose is much smaller, un- 

 less it is administered after a considerable interval of time. In the 

 birds pituitary extract causes a fall of blood pressure, which is anta- 

 gonised by adrenaline and by barium (Paton and Watson [1912]). 

 The powerful stimulation of uterine plain muscle was first pointed out 

 by Dale [1909] and also studied by von Frankl-Hochwart and 

 Frohlich [1910] and was first applied clinically by Bell [1909] in 

 England and soon afterwards by Foges and Hofstatter in Germany. 

 The supposed pure substances have been used clinically by Herzberg 

 [I9I3J 



