TOO THE SIMPLER NATURAL BASES 



diabetic effect of the natural 1-variety. The minimal dose of the latter 

 which produces glycosuria in rabbits of 2 kilos, is O'4-O'5 mg. 



D. Toxic Action of Adrenaline. 



The effects which have so far been described are all brought about 

 by minute doses of adrenaline. Larger, although still quite small 

 doses cause death, and adrenaline is therefore a powerful poison. For 

 guinea-pigs, rabbits, and dogs the fatal intravenous dose is about one- 

 tenth to one-quarter of a milligram per kilo, of body weight. For cats 

 the corresponding dose is O'5-O'8 mg. per kilo. The subcutaneous 

 lethal dose is very much higher; for white rats Cushny [1909] 

 found 10-20 mg. per kilo, and Schultz [191)9, i] for mice 8 mg. 

 per kilo, of body weight. For guinea-pigs the corresponding dose is 

 10 mg. According to Crawford [1907]. For the toxicity to dogs and 

 cats, reference may also be made to Lesage [1904, I, 2]. 



The Physiological Action of Dextro- and of Racemic 

 Adrenaline. 



Cushny, who discovered the difference in the physiological activity 

 of optical enantiomorphs in the case of hyoscyamine and hyoscine, 

 also first drew attention to the quantitative^ differences in the action 

 of natural 1-adrenaline and the synthetic racemic substance. 1 He 

 [1908] found racemic adrenaline to be about half as active as the 

 natural variety and concluded therefore that d-adrenaline is inactive. 

 Later [1909}, having at his disposal a specimen of the dextro-variety, 

 he was able to estimate its activity directly, instead of by difference, 

 and he slightly revised his preliminary conclusion. The specimen of 

 d-adrenaline examined had yVrV f the activity of 1-adrenaline in 

 raising the blood pressure of dogs and cats. The ratio of the pressor 

 activities of racemic and natural adrenaline is therefore not I : 2 but 

 between 13 : 24 and 16 : 30. The ratio of the activities of the two 

 isomer.ides in producing glycosuria was very similar, namely I : 12-18, 

 and the minimal lethal doses for white rats were in about the same 

 ratio. 



The different physiological activity of the two enantiomorphous 

 adrenalines has also been dealt with in a series of papers by Abder- 

 halden, in collaboration with Miiller [1908], Thies [1909], Kautzsch 

 [!99]i Slavu [1909], and Kautzsch and Miiller [1909]. Some 

 of the conclusions arrived at are that 1-adrenaline is fifteen times as 



1 Cf. Dixon, Pharm. Journ., 1908, XXVI, 723 ; Biberfeld, ibid., p. 626 ; Cushny, 

 ibid., p. 668. 



