THE PHARMACOLOGICAL ACTION OF PROTOCATECHYL-TROPEINE. 



281 



animal, both phrenic nerves were cut and the respiration registered by a connection 

 with the tracheotomy tube. On injecting 0"01 g. protocatechyl-tropeine hydrochloride 

 into the external jugular vein the respiration ceased thirteen seconds after the 

 commencement of the injection (fig. 6). 



In connection with the production of temporary cessation of the respiration, the 

 question of dose is of paramount importance. The concentration of the drug producing 

 this effect in the blood supplying the medulla can apparently vary only within narrow 

 limits. Hence not only the amount of drug injected but also the time occupied by the 

 injection is of moment. This explains why the effect does not result from hypodermic 

 or intraperitoneal administration. It is probably owing to this fact that the effect has 

 not been observed more frequently. It can certainly be produced by a number of 



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Fig. 6. — Effect of O'Ol g. protocatechyl-tropeine hydrochloride on respiration of rabbit with both phrenic nerves divided. 

 Tracing taken as fig. 5, but with air-exits closed. Time in seconds. 



drugs, but the doses of those which induce it fall within very narrow limits. In many 

 of these cases the effect is probably merely that of a protoplasmic poison, and the 

 respiration is most obviously affected because the respiratory centre is the most 

 sensitive of the medullary centres to this class of substances. This hypothesis, however, 

 does not seem sufficient to explain the actions of the substances already mentioned. 



In a preliminary report on the physiological action of pukateine, an alkaloid 

 isolated by Aston * from pukatea bark, Malcolm says : " Intravenous injection of 10 mg. 

 into an anaesthetised rabbit caused sudden stoppage of respiration without convulsions : 

 the heart continued to beat vigorously for a long time afterwards." As Mr Aston 

 had given me some years ago a specimen of the mixed alkaloids isolated by him from 

 pukatea bark, I was able to investigate this point. The alkaloids were first converted 

 into the hydrochlorides. On injecting 0*01 g. intravenously (time occupied by 

 injection, seven seconds) into a rabbit (wt. 2100 g.) the respiration was not 



* Annual Rep., New Zealand Dept. of Agriculture, 1908, Chemistry Division, p. 226. 

 TRANS. ROY. SOC. EDIN., VOL. XLYII. PART II. (NO. 12). 42 



