342 Lee 



twitch. This has been aheady shown and commented on by Dixon (3;. 

 Moreover, these flrut^s differ in their action from strychnine in that, wliilst 

 this drug affects the sensory cells so that the convulsions can onl}' l)e pro- 

 duced by an appropriate afierent stimulus, the drugs under C(jnsideration act 

 on the motor cells. This is proved, first, because on being applied to the 

 cord they produce immediate twitchings of the muscles which are supplied 

 by that section of the cord ; second, because they are not reflex in origin : 

 and third, because the twitchings are limited to the cells affected. That is 

 to say, str3^chnine applied to one small portion of the cord produces con- 

 vulsions over the whole body ; but nicotine applied in the same way causes 

 twitchings only in the muscles supplied by the corresponding part of the 

 affected cord. 



(b) On the Circulatory System. — Pyridine produces remarkably little 

 effect ; in fig 4, A, 5 c.c. of a 1 per cent, solution were slowly injected and 

 produced practically no alteration in the blood-pressure, nor in the general 

 condition of the circulation. Collidine, however, in small doses cause,s 

 considerable dilatation of the blood-vessels, and a corresponding fall in 

 blood -pressure. This is shown in fig. 4, B, in which the upper tracing 

 represents intestinal volume, and the lower the blood-pressure. It will be 

 noticed that as the vessels dilate the pressure falls. In this case, however, 

 there can be no doubt that some of the fall of pressure is due to cardiac 

 depression. Larger doses of collidine weaken the heart, and consequently 

 lower the blood-pressure to such an extent that the intestinal vessels, instead 

 of filling with blood, shrink, secondarily to the fall of blood-pressure. 



The effect of nicotine is shown in fig. 4, C, for the sake of comparison. 

 It also lowers the blood-pressure, as shown in the second (detached) part of 

 the tracing, but only after an initial rise, I shall have occasion later, in 

 dealing with the action of tobacco smoke on man, to refer again to this well- 

 known rise followed by a fall in blood-pressure. 



IV. Toxicity a.s estimated by Injection into Intact Animals. 



The relative toxicity of pyridine, collidine, and nicotine was estimated 

 by determining the minimal lethal doses in frogs. 



Three frogs, each within a fraction of 23 grams in weight, were 

 injected with solutions containing a quarter of a grain of each drug 

 respectively. The injections were made into the dorsal lymph sac. 



During the two hours after injecting pyridine the animal was very 

 active, the pupils were dilated, and respirator}^ efforts were increased; there 

 was no paralysis. 



The second frog, after collidine, became paralysed in two minutes, 

 respiration almost ceased, the pupils were widely dilated, and reflexes were 

 entirely absent. After a lapse of twenty minutes feeble respiratory 

 movements became evident, and the animal gradually recovered. 



Nicotine was much the most toxic. The frog died about two minutes 



