49 
millimeters mercury, or a fall of 42 per cent (fig. 8). The obvious 
conclusion, therefore, is that antipyrine either depresses the vaso- 
motor center or dilates the peripheral vessels from a local action, 
and both factors may play some part in this marked fall in pressure. 
The decrease in the heart rate is not prevented by paralysis of the 
vagi, and would be due, therefore, to a direct depression of the 
heart muscle. 
Caffeine was injected coincident with and also subsequent to the 
injection of antipyrine, but appeared to he devoid of any antagonistic 
action upon either the depressant effect of antipyrine on the strength 
of the heart or upon the blood pressure. As a matter of fact, when 
caffeine was injected at the time when the heart was most depressed 
or just beginning to recover from the antip}^rine, caffeine appeared 
to delay the recovery or to cause a secondary weakening in both the 
heart strength and the blood pressure. Some antagonism was shown 
upon the heart rate which was restored to normal by the caffeme 
injections. 
GENERAL TOXIC ACTION. 
The general toxic effect of antipyrine and mixtures containing 
antipyrine when given hypodermicalty to mice was the subject of 
a further series of experiments. The easy solubility of antipyrine 
in water obviated the introduction of the additional factor, alco- 
hol, into the problem, as in the case of acetanilide. The drug was 
given by the method already described and the minimum lethal 
dose determined. This was found to be 0.0010 gram, wliich amount 
caused death in about half an hour. By comparison, it will be 
noted that this is not only a smaller dose than was required in the 
case of acetanilide, but also that the time the animal survived was 
much shorter. The reason for tliis apparently greater toxicity (upon 
the frog’s heart about seven times less toxic) when compared with 
acetanilide is probably dependent upon the relative solubility of the 
two drugs in the fluids of the tissues, and hence upon the rate of their 
absorption. Table IV gives protocols showing the determination of 
the minimum lethal dose for this drug. 
Table IV. — Minimum lethal dose of antipyrine for white mice, hypodermic injection. 
[— = survived; += death.] 
! 
Weight. 
! 
Dose. 
Result. 
Minutes 
1 till death. 
14. 33 
0. 0008 
20. 00 
. 0008 
— 
19. 70 
. 0009 
_ 
17. 17 
. 0010 
+ 
30 
19. 92 
.0010 
+ 
80 
15. 47 
.0011 
+ 
25 
18. 89 
. 0012 
+ 
35 
176— Bull. 53—09 4 
