236 SCIENCE PROGRESS 



active substance might be related to histidine. As a number of 

 decarboxylated amino-acids had already been found in ergot 

 and at least one of these was physiologically active, it was 

 probable that the principle acting on the isolated uterus was 

 iminazolylethylamine ; that this was indeed the case was proved 

 by the isolation and analysis of the base from ergot and by 

 comparing it with the base from histidine. 



It was in this way that attention was first drawn to the 

 physiological activity of iminazolylethylamine. About the 

 same time Kutscher {Zentr. Physiol. 1910, 24, 163) succeeded 

 in obtaining a compound from ergot which most probably 

 was the base under consideration but he failed to identify 

 it with the putrefaction base from histidine. 



Histidine, like all amino-acids, is physiologically inert but 

 the base which is formed by depriving it of the carboxyl group is 

 among the most powerfully active crystalline substances known: 

 one-tenth of a milligram added to a guinea-pig's uterus in a bath 

 of 250 c.c. generally suffices to produce a maximum contraction. 

 The effect of even one part in 25o;millions of Ringer's solution 

 is often quite definite. When injected intravenously in small 

 doses the base causes a marked fall of blood-pressure in a dog 

 or cat ; less than one milligram will kill a guinea-pig. A peculiar 

 feature of the action is that although the systemic arterioles 

 dilate, those of the lungs contract ; this would appear to 

 be the pharmacological justification for the use of ergot in 

 phthisis, as practised by many clinicians. 



Although iminazolylethylamine is formed during putre- 

 faction and although the base is formed during the lengthy 

 processes of extraction and dialysis in the preparation of 

 some ergot extracts, a certain amount is undoubtedly present 

 in ergot as such. Kutscher obtained his base by extracting 

 ergot with boiling water; Barger and Dale tested an extract 

 of ergot within half an hour of collecting the ergot in the 

 field and found it to be distinctly active. 



As the isolation of the base from ergot or from a putrefaction 

 mixture is troublesome, it became desirable to have some other 

 method of preparing the base. It is not possible to obtain 

 the base from histidine by merely heating it but a fair yield may 

 be got by heating with sulphuric acid in sealed tubes (Ewins 

 and Pyman, Journ. Chem. Soc. 1911,99,339). A better method 

 is afforded, however, by the synthetic process devised by 



