PHARMACOLOGICAL ACTION OP TETR A- ALKYL- AMMONIUM COMPOUNDS. 35 



had completely recovered from the paralysis ; but even in these cases the depression or 

 paralysis of the motor nerve-endings and of the respiration was shown to run a parallel 

 course. When the influence of tetra-methyl-ammonium chloride on the terminations 

 of the phrenic nerves was investigated, complete agreement was found to exist between 

 their irritability and the effect on the respiration. In these experiments the phrenic 

 nerves were isolated in the base of the neck and one or other, usually the right, 

 stimulated in continuity. The respiration was recorded by means of a phrenograph 

 connected to a tambour recorder. A considerable number of such experiments were 

 made, but as they all conform to that shown in fig. 1, it is only necessary to refer to 

 this. In this experiment the right musculo-cutaneous and right phrenic nerves were 

 stimulated simultaneously. As will be seen from the tracing (line R), the effect on 

 the respiration and the effect of stimulating the phrenic are completely concordant. 



It would seem therefore that the respiratory paralysis produced by tetra-methyl- 

 ammonium chloride is largely, if not solely, due to paralysis of the nerve endings in 

 the respiratory muscles. This being the case, we might expect a comparable effect to 

 be given by curare. This substance, however, is somewhat slower in its action and 

 much more prolonged in its effects than tetra-methyl-ammonium chloride, and after 

 the injection of doses sufficient to paralyse the respiration spontaneous recommencement 

 of the breathing cannot be obtained without artificial respiration. According to Tillie,* 

 the smallest dose of curarin, administered intravenously, which will completely paralyse 

 a rabbit is 0*2 mg. p. kg. body-weight; 0*3 mg. to 0*5 mg. p. kg. cause loss of reflexes 

 and spontaneous breathing for ten to fifteen minutes. Consequently in an experiment 

 on a cat — animals which, according to BoEHM,t are somewhat less sensitive to curarin 

 than rabbits — carried out in a similar manner to those referred to on p. 18, anaesthesia 

 being maintained throughout the experiment, a dose of 0"16 mg. p. kg. body-weight 

 was decided on. The intravenous injection of this quantity of curarin caused gradual 

 failure of the respiration commencing twenty-one seconds after the beginning of the 

 injection and going on to complete paralysis two minutes later. Electrical stimulation 

 of one of the cords of the brachial plexus and of the right phrenic nerve showed 

 gradually diminishing contraction of the fore limb and the diaphragm respectively 

 pari passu with the failure of the respiration. With complete cessation of the 

 respiration stimulation of the phrenic nerve caused no contraction of the diaphragm, 

 but stimulation of the brachial cord produced a just appreciable movement of 

 the limb4 Artificial respiration was performed, and five minutes later spontaneous 

 breathing recommenced, but even with the aid of short periods of artificial respira- 



* Arch.f. exp. Path. u. Pharm., xxvii. p. 22 [1890]. 



t Festschrift zu G. Ludwig's 70. Geburstag, 1886, quoted by Tillie, loc. cil., p. 4. 



% This result although slight is probably unusual. By careful dosage of curarin Tillie was able to keep an 

 animal paralytic without stopping the respiration ; and A. Mosso (Memoria della R. Acad, delle Scievza di Torino, ser. 

 ii. vol. liii. p. 397, 1903) and M. Chio (Arch, di Farmacol. speriment. e Scienz. affin., xii. p. 533, 1912), by comparing 

 the respiratory movements of the thorax and abdomen, have shown that the muscles of the thorax are paralysed 

 before those of the diaphragm. 



