PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 33 



33 mm. Hg one minute after the injection. It showed practically no 

 recovery. 

 4.0^. 1 mg. injected. A rapid increase in depth and frequency occurred seven seconds 

 after the beginning of the injection. Seven seconds later the frequency, 

 and ten seconds later the depths of the respiration, began to diminish, and 

 forty-five seconds from the commencement of the injection respiration 

 ceased. After twenty seconds a few shallow respirations occurred at 

 intervals during the next half-minute. The blood-pressure very gradually 

 fell to 15 mm. Hg. 

 Cause of the Respiratory Paralysis. — As previously stated, Iodlbauer # ascribes 

 the temporary paralysis of the respiration to stimulation of the terminations of the 

 fifth cranial nerves in the nose. He came to this conclusion because (l) he observed 

 closure of the glottis— an associated act of the Kratschmer-Hering reflex — during the 

 respiratory standstill ; (2) he was unable to produce respiratory paralysis after anaesthetis- 

 ing the nasal mucous membrane ; (3) he did not observe the characteristic effect in 

 cats, animals in which the typical Kratschmer-Hering reflex is absent. In these 

 animals he obtained transient powerful stimulation of the respiration followed by some 

 depression and rapid return to the normal. 



It is difficult to understand why Iodlbauer failed to obtain the respiratory 

 paralysis in cats. It is possible that the animal used for the experiment in which 

 efficient doses were given may have been relatively insusceptible to tetra-methyl- 

 ammonium chloride, since variations in the reaction to this substance occur in these 

 animals and also in rabbits. In the few experiments I have made on cats, respiratory 

 paralysis has been as easily induced as in rabbits, although generally somewhat larger 

 relative doses were necessary for the purpose (see fig. l). 



Nor have I been able to corroborate Iodlbauer's statement that anaesthetising 

 the nasal mucous membrane of rabbits prevents the appearance of the respiratory 

 paralysis. Even after the careful injection of large quantities of a 5 per cent, solution 

 of cocaine hydrochloride so as to reach the whole mucous membrane, the intravenous 

 injection of 1 mg. tetra-methyl-ammonium chloride produced the same effect as before 

 the application of the cocaine. 



It would seem further that if this action is due to stimulation of the trigeminal 

 nerve-endings in the nose, the local application of such a diffusible substance as tetra- 

 methyl-ammonium chloride would induce it. As I shall show in a later communication, 

 the application of 1 in 5000 solutions of this substance to frogs' muscles produces a 

 maximal effect within a few seconds, and it is inconceivable that the nasal mucous 

 membrane should act as a semi-permeable membrane to it. Yet the injection of 1 to 2 

 per cent, solutions into the nasal cavities of anaesthetised animals, the respiration of 

 which was paralysed by intravenous injections of 1 mg., produced no effect whatever. 

 Iodlbauer apparently used this method with equivocal results, which he attributes to 



* hoc. cit. 

 TRANS. ROY. SOC. EDIN., VOL. L. PART I. (NO. 2). • 5 



