CHOLINE AND ALLIED SUBSTANCES 63 



depressant action observed by others was the result of an impurity. 

 Popielski [1910, i], in whose laboratory Modrakowski carried out his 

 experiments, shares the latter's views, but Mott and Halliburton's 

 statement that choline has primarily a depressent action has been 

 confirmed by Busquet and Pachon [1909], Abderhalden and Muller 

 [1910, 1911], Mendel and Underbill [1910], Pal [1910, 1911], Muller 

 [1910], Lohmann [1907, 1908], and most recently by Mendel, Under- 

 bill and Renshaw [1912]. 



The general conclusion is that Modrakowski's and Popielski's aber- 

 rant results are not to be explained by impurities in the choline em- 

 ployed by others, but rather to differences in anaesthesia and dosage. 

 With small doses up to I mg. per kilo, in dogs and cats under ether 

 or urethane, a fall of blood pressure always results, which with some- 

 what large doses may be followed by a slight rise. Larger doses, es- 

 pecially when repeated, may at once exert a pressor action. With 

 slight anaesthesia, or with the medulla oblongata cut, small doses may 

 also produce a rise of blood pressure. 



The depressent action is partly due to an effect on the heart and 

 partly to vaso-dilatation in the limbs and splanchnic area. After 

 atropine, perfusion of an isolated organ produces only vase-constriction. 

 According to Muller this vaso-motor reversal depends on a paralysis 

 by atropine of the dilator elements of the vascular walls, and resembles 

 the adrenaline vaso-motor reversal by ergotoxine (Dale [1906, Ch. VI]). 



Choline has a stimulant effect on the isolated muscle of the in- 

 testine, uterus and iris, resembling in this respect physostigmine some- 

 what closely. It further stimulates the secretion of the lachrymal, 

 salivary, and sweat glands. Salivation is one of the first symptoms of 

 choline poisoning in an intact animal (Brieger). The physiological 

 activity of choline is, however, slight, only about T V^j of that of 

 neurine. The minimal lethal dose for rabbits of I kilo, is 0*5 grm. 

 according to Brieger, but Mott and Halliburton were unable to kill an 

 animal by choline injections. Compare also Riesser [1913; Ch. V, 

 creatine]. 



The action of choline on isolated nerves and the excised heart of 

 the frog has been studied by Waller and Sowton [1903]. 



Hunt and Taveau [1911] have studied the action of a large number of synthetic 

 choline-like substances and their derivatives. In particular acetyl-choline 



(CH 3 ) 3 N(OH) . CH 3 . CH 3 . O . OC . CH, 



is remarkable in being 100,000 times as depressent as choline itself. According to Mr. A. 

 J. Ewins [Bio-Chem. J., 1914, 8, 44] acetyl choline is present in small quantity in some ergot 

 extracts. The lower homologue formocholine (CH 8 ) 8 N(OH) . CH a OH is also more active 

 than choline. The nitrous acid ester of choline is identical with Schmiedeberg and 

 Harnack's /sfo-muscarine (see p. 68). 



