510 PROFESSOR C. R. MARSHALL ON THE 



that tetra-ethyl-ammonium chloride in large doses produces paralysis of the myo-neural 

 junction, the want of parallelism between the pharmacological activity of and number 

 of methyl groups in these compounds does not lend any support to the view that the 

 activity is associated with the methyl groups. The most striking change occurs in the 

 passage from tri-methyl-ethyl-ammonium chloride to di-methyl-di-ethyl-ammonium 

 chloride. Tri-methyl-ethyl-ammonium chloride possesses a degree of toxicity and 

 activity not far removed from that of tetra-methyl-ammonium chloride, but the 

 replacement of another methyl group by ethyl, thereby forming di-methyl-di-ethyl- 

 ammonium chloride, causes a marked fall in toxicity and pharmacological action. 

 This particular instance might be explained on Werner's view * of the constitution 

 of quaternary compounds, but it would not so readily explain the differences in 

 pharmacological action observed in the other members of the series, nor the fact that 

 in the methyl-ammonium compounds investigated by Brunton and Cash f the 

 greatest change in pharmacological activity occurs on passing from tetra-methyl- 

 ammonium salts to tri-methyl-ammonium salts. The variations in pharmacological 

 activity might, however, be explained by assuming different values for the hydrogen 

 atoms of the ammonium radical, but although the successive hydrogen atoms are 

 replaceable with varying ease, there does not seem to be sufficient evidence for 

 believing that alkyl groups once introduced are of varying value. The order in 

 which such groups are introduced does not appear to have any effect on the resultant 

 compound.} The chemical characters of the methyl-ethyl-ammonium compounds 

 make it improbable that the methyl and ethyl radicals act independently pharmaco- 

 logically, and it may be mentioned that Rosenstein § concluded that the pharmaco- 

 logical activity of quaternary compounds was not due to the presence of special 

 radicals. 



Meyer || is of opinion that saturation of the nitrogen by a hydroxy 1 and four 

 hydrocarbon radicals is alone of importance ; and Hildebrandt H that, as regards the 

 action of ammonium bases, the curare-like action depends on the manner in which 

 the fifth (not hydrocarbon) valency of the nitrogen is saturated. But a pentad 

 valency of the nitrogen or, as the action is also produced by phosphonium ## and 

 arsonium ft bases, of other corresponding atoms is not necessary, and neither of these 

 views affords any explanation of the very slight activity of tetra-ethyl-ammonium 

 chloride. This is equally true of Fraenkel's hypothesis. Fraenkel $. concludes that 

 the paralysing action on the end-plates is caused, not by a certain elementary com- 

 position or the presence of certain radicals, or by certain elements serving as a centre 



* New Ideas of Inorganic Chemistry, p. 30. For other views see Meisenheimer, Liebig's Annalen, vol. cccxcvii. 

 p. 273 [1913] ; vol. cccxcix. p. 371 [1913] ; Fromm, ibid., p. 366. 



t hoc. cit. % Cf. Singh, Trans. Chem. Soc, ciii. p. 604 [1913]. 



§ Compt. rend., cxxx. p. 752 (1900). 



|| Ergebnisse der Physiologie, i. pt. ii. p. 199 [1902]. IT Neuere Arzneimettel, 1907, p. 134. 



** Vulpian, Arch, de physiol. norm, et path., i. p. 472 [1868] ; Lindemann, Arch. f. exper. Path. u. Pharmak., 

 xli. p. 191 [1898]. +t Bcergi, Path.f. exper. Path. u. Pharmak., lvi. p. 101 [1906]. 



\\ Ergebnisse der Physiologie, iii. pt. L p. 307 [1904]. 



