PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 507 



isotonic solution, it is found to retain a considerable degree of irritability after the 

 corresponding muscle of the opposite side, similarly treated, but rhythmically 

 stimulated, has ceased to contract. The several substances showed relatively little 

 difference in toxic power when compared in solutions of the same molecular strength. 



Remarks. 



The most important action of these quaternary ammonium compounds is that 

 associated with the myo-neural junction. Since the work of Crum Brown and 

 Fraser # paralysis of the motor nerve-endings has been recognised as a fundamental 

 action of quaternary compounds, and although a large number of such compounds 

 of varied composition have been examined, very few have been described as wanting 

 this action in some degree. Crum Brown and Fraser t themselves found that 

 nicotine meth-iodide and metho-sulphate were very slightly active, and concluded 

 that they do not paralyse the motor nerve endings, since the reflexes obtained in a 

 protected limb and in a limb exposed to the action of the substances were of 

 approximately equal strength. In the later stages of the intoxication, however, 

 they "appeared to be of greatest strength in the non-poisoned limb." J The latter 

 observation seems to me of significance in view of the later investigation of 

 Buchheim and Loos,§ who found that after the injection of 27 mg. or more per 

 gramme of frog the sciatic nerve became unirritable, while the muscles still reacted 

 to stimulation. The only other paper with which I am acquainted mentioning 

 quaternary compounds which do not paralyse motor nerve endings is by Pohl.|| 

 He investigated certain quaternary papaverine derivatives — papaverine metho- 

 chloride, papaveraldine metho-chloride, and papaverinol etho-chloride — which, he 

 says, do not produce, in frogs, any curare-like action. Unfortunately he gives no 

 experiments on which the statement is based. As these substances produce a 

 temporary paralysis of the respiration similar to that produced by tetra-methyl- 

 ammonium chloride, I decided to reinvestigate the point. Papaverine meth-iodide 

 was prepared by heating a 1 in 30 alcoholic solution of papaverine with slightly 

 more than a molecular quantity of methyl-iodide on a water-bath under a reflux 

 condenser for six hours, afterwards distilling off the slight excess of methyl-iodide, 

 decolorising with charcoal, and crystallising and recrystallising from diluted alcohol 

 or water. A determination of the iodine showed that it was pure. The substance 

 tested on a gastrocnemius-sciatic preparation in a manner similar to experiments 

 previously described was found to paralyse the nerve-endings before the muscle. 

 The effect of a 1 in 350 solution in Ringer's fluid is shown in fig. 23. As will be 

 seen, the nerve-endings were paralysed in nine minutes, the muscle at this time and 



* Trans. Boy. Soc. Edin., xxv. pp. 151, 693 [1869] ; Proc. Soy. Soc. Edin., vi. p. 556 [1869]. 



t Trans. Roy. Soc. Edin., xxv. p. 187 [1869]. 



X Lot. cit., p. 191. 



§ Eckhard's Beit. z. Anat. u. Physiol., v. p. 226 [1870]. 



|| Arch, internat. de pharmacod., xiii. p. 479 [1904]. 



