PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 511 



for a spatial arrangement, but is solely dependent on the manifestation of two 

 potential valencies, which give a certain different orientation in space to the radicals 

 bound to them, independently of the number of chief valencies otherwise present and 

 of their spatial orientation. It is possible that the differences in pharmacological 

 action shown by tetra-methyl and tetra-ethyl-ammonium chlorides may be associated 

 with differences in intra-molecular ionisation, but so far no data relating to these 

 compounds are available. 



With regard to the place and mode of action of substances producing peripheral 

 paralysis there is some difference of opinion. Regarding the place of action two 

 views are held : (l) that it is the nerve-endings or motor end plates, (2) that it is an 

 intermediary substance in functional connection with the nerve-endings on the one 

 hand and with the contractile tissue of the muscle on the other. The intermediary 

 substance, which is conveniently referred to as the myo-neural junction, is variously 

 regarded as a synapse, a specialised tissue of high irritability, or a part of the muscle 

 cell itself with special chemical reactivities. As the general question of the place of 

 action of these substances has been dealt with by Langley * in the Croonian Lecture 

 of 1906, and more recently by Dixon and Ransom t in an article in the Ergebnisse 

 der Physiologie, it is only necessary to refer to papers bearing immediately on the 

 present investigation. 



Much of the more recent work on this question has been done by Langley,} who, 

 from his investigations with nicotine and curare, has come to the conclusion that 

 the action is upon what he terms " receptive substance," which forms part of the 

 constituents of the muscle cell. Nicotine in certain concentrations when applied to 

 an isolated muscle produces two distinct effects, namely, an immediate contracture 

 followed by a fall, and, a second later, slower and more prolonged contracture which 

 passes into rigor. Small concentrations produce only the primary contracture ; 

 large concentrations may fuse the two effects. Langley attributes the primary 

 contracture to an action on the receptive substance, the later contracture to an 

 effect on the contractile substance proper of the muscle. My own experiments 

 with nicotine, which, however, have not been numerous and have been almost limited 

 to the effects on the excised sartorius of concentrations of 0'18 per cent, in Ringer's 

 fluid, corroborate those of Langley, and have suggested a comparison with the 

 effects obtained with tetra - methyl - ammonium chloride and tri - methyl - ethyl - 

 ammonium chloride. The early contracture obtained with nicotine has so closely 

 simulated the contraction produced by tetra-methyl-ammonium chloride as to suggest 

 that the mode of action of the two substances in this respect is identical. And that 

 this is probably the case is shown by the fact that if a nicotine solution of sufficient 



* Proc. Roy. Soc. Lond., lxxviii., B, p. 170 [1906]. See also Journ. of Physiol, xlviii. p. 103 [1914]. 



+ Ergebn. d. Physiol, xii. p. 765 [1912]. Also Dixon, Proc. Roy. Soc. Med., v. (Therap. and Pharmacol, sect.), 

 p. 1 [1911]. 



I Loc. cit. ; also Journ. of Physiol, xxxvi. p. 347 [1907] ; xxxvii. pp. 165, 285 [1908] ; xxxix. p. 235 [1909] ; 

 xlvii. p. 159 [1913] ; xlviii. p. 73 [1914]. 



