CHOLINE AND ALLIED SUBSTANCES 65 



Schmiedeberg's base was isolated as the gold salt which Harnack 

 [1875] found to be contaminated with choline ("amanitine ") auri- 

 chloride ; a separation was effected by crystallisation from hot water, 

 the muscarine salt being the more soluble. Harnack found muscarine 

 aurichloride to have the composition C 5 H 14 O 2 N . AuCl 4 ; the base 

 therefore differs from choline in having an additional oxygen atom. 

 Soon afterwards Schmiedeberg and Harnack [1877] obtained a base 

 of this composition by heating dried choline chloride with con- 

 centrated nitric acid on the water bath ; the new base was isolated as 

 the platinichloride ; the chloride, when left in a desiccator, sets to 

 a crystalline mass and the base has according to Schmiedeberg and 

 Harnack the constitution (CH 3 ) 3 : NCI . CH 2 . CH(OH) 2 , being 

 therefore a hydrated aldehyde like chloral hydrate (but compare 

 addendum, p. 68). 



This synthetic, artificial, or flseudo-muscarinQ is chemically very 

 similar to the natural substance, and the physiological resemblance is 

 sufficiently close to have induced Schmiedeberg and Harnack to believe 

 in the identity of the two bases. Boehm [1885, 2] was the first to 

 point out the differences in the physiological action. He found that 

 ^ mg. of flseudo-muscarine (from choline) was required to stop the 

 frog's heart in diastole, whereas the corresponding dose of natural 

 muscarine is only ^VsV m g-> according to Schmiedeberg and Harnack. 

 Recently this large difference in the activities of the two bases has been 

 confirmed in Schmiedeberg's laboratory by Honda [1911], who again 

 prepared natural muscarine and found it active on the frog's heart in 

 doses of ^VrV mg., according to the season of the year, whereas the 

 same effect was only produced by -J-i-J mg. of ^seudo-muscarme from 

 choline. Boehm further found that in larger doses (10 mg.) pseudo- 

 muscarine produces a curare-effect in mammals, which is not given 

 even by large doses of the natural base ; moreover there is no com- 

 plete antagonism between pseudo-muscanne and atropine : cats which 

 have been poisoned by pseudo-muscanne cannot be kept alive by a 

 subsequent dose of atropine. The curare-like action of pseudo- 

 muscarine on frogs is according to Boehm fifty times as great as that 

 of choline from which it is derived (the minimal paralytic doses being 

 O'l and 50 mg.), and according to Honda [191 1] flseudo-muscarine 

 has one-fifth of the activity of pure curarine in this respect. According 

 to H. Meyer (see below) pseudo-m\\scarmz causes contraction of the 

 pupil in birds, natural muscarine does not. 



Another synthetic substance, much more distantly related to 

 muscarine than the oxidation product of choline, is trimethylamino- 



5 



