LOCAL ANESTHETICS 351 



phrenograph or, in two cases only, by a tambour connection 

 to the exit tube of the tracheal cannula. The drug, dissolved 

 in normal saline, was injected into the right anterior facial 

 vein. As the degree of concentration of the drug in the blood 

 in the heart and the medulla is a very important factor in this 

 kind of experiment, care was taken to make the injections in 

 each experiment as uniform in duration as possible, and, to 

 obtain this, different dilutions of the different drugs were 

 employed. 



The substances investigated were cocaine, tropacocaine, 

 /3.eucaine, holocaine, stovaine, alypine, nirvanine, and novo- 

 caine. They all produce, when administered in sufficient 

 quantity, diminution in the extent and slowing of the respira- 

 tion, and almost invariably a fall of blood-pressure. In 

 relatively small doses cocaine, and to a less extent and less 

 constantly stovaine, cause a rise in blood-pressure, but in 

 such doses the respiration is not as a rule materially affected. 

 On the other hand, large doses (0*003 g.) of the more potent 

 drugs, such as cocaine and alypine, cause almost immediate 

 cessation of the respiration and a marked and rapid fall of 

 blood-pressure, and the animal quickly dies. For the purpose 

 of comparing the relative action of these compounds, it is 

 desirable to employ doses producing distinctive effects from 

 which complete or considerable recovery occurs. This allows 

 of repeated doses of different drugs being given to the same 

 animal ; and this is especially necessary because, as previous 

 observers have shown and the same was noted in my own 

 experiments, different animals often react somewhat differ- 

 ently, at least quantitatively, to this class of drugs. 



An analysis of the tracings obtained seems to show that, 

 as regards their effect on the circulation and respiration, the 

 order of toxicity, commencing with the most potent, is 

 (a) cocaine ; (6) alypine ; (c) holocaine, stovaine, tropacocaine ; 

 (d) /3-eucaine ; (e) nirvanine and novocaine. And if, following 

 Le Brocq, numerical values may be ventured upon, the relative 

 toxicity of the various substances may be said to be approxi- 



