30 THE SIMPLER NATURAL BASES 



the contraction due to /3-iminazolylethylamine is permanently abolished 

 by adrenaline, which is not so in the intact animal. Large guinea- 

 pigs are killed in .a few minutes by an intravenous injection of 

 O'5 mg., owing to asphyxia resulting from the constriction of 

 the bronchioles ; post-mortem the lungs are found to be permanently 

 distended. This corresponds closely to the effects of poisoning 

 by Witte's peptone and the toxic effects of serum or other protein 

 in the sensitised guinea-pig, known as anaphylactic shock. Unlike 

 peptone, iminazolyl-ethylamine does not, however, possess in any 

 marked degree the power of rendering the blood incoagulable. Ac- 

 cording to Popielski the physiological effect of peptone is produced by 

 a hypothetical substance " vasodilatin," and he [1910, 2] has suggested 

 that iminazolyl-ethylamine acts by liberation of vasodilatin, when 

 injected intravenously, a supposition rejected by Dale and Laidlaw 

 [1911]. Attention may also be drawn to a possible connection 

 between iminazolyl-ethylamine and the " depressor substances " of 

 various observers, such as the urohypotensine of Abelous and Bardier 

 [1909]; the depressent action of Bayliss and Starling's secretine is 

 indeed explained by the isolation from it of iminazolyl-ethylamine 

 by Barger and Dale [1911]. 



The resemblance of the symptoms of poisoning with iminazolyl-ethyl- 

 amine to those of anaphylactic shock is indeed very striking (Dale 

 and Laidlaw [1910, 1911], Pfeiffer [1911], Biedl and Kraus [1912], 

 Schittenhelm and Weichardt [1912], Aronson [1912], Friedberger 

 and Moreschi [1912]); not only does it extend to the bronchial 

 constriction in guinea-pigs, mentioned above, but also to a fall of body 

 temperature, which is one of the characteristics of the milder degree 

 of the " shock ". Thus the intraperitoneal injection of 3 mgs. of 

 iminazolyl-ethylamine was found by Dale and Laidlaw to lower the 

 rectal temperature of a guinea-pig gradually from 38-5 to 28-5 in the 

 course of two hours ; next day it was again 38. Extremely minute 

 doses of serum may, on the other hand, cause a rise of body temperature 

 in an anaphylactic animal, and the same applies to iminazolyl-ethylamine 

 when given in sufficiently small doses to a (normal) guinea-pig, as 

 has been shown by Pfeiffer [1911]. The correspondence is also illus- 

 trated by the relatively great resistance of dogs, both to anaphylactic 

 shock and to the amine. In this connection we may refer to a paper 

 by Engeland [1908, 3] in which evidence is adduced that histidine 

 derivatives are more readily broken down by carnivora than by 

 herbivora. No data are available to fix the lethal dose of /3-iminazolyl- 

 ethylamine in man, but a Macacus monkey of 1-25 kilo, was killed by 



