PART II. 
THE TOXICITY OF ANTIPYRINE MIXTURES. 
Although it is now generally recognized that antipyrine is less toxic 
than acetanilide® it has never been so popular as an ingredient of 
headache mixtures. It is occasionally dispensed with other drugs, 
however (as in bromopyrine for example), and accordingly a series 
of experiments were made to determine whether these altered its 
toxicitv. 
ACTION UPON THE FROG’S HEART. 
The method used to determine the effect of antipyrine and mix- 
tures of antipyrine upon the frog’s heart was the same as that described 
for acetanilide, page 13. The species of frog and the various precau- 
tions used to obtain uniform results were also the same. 
Although affecting the frog’s heart when perfused through it in 
much the same way as acetanilide, antipyrine is much less toxic to it. 
This ratio is about 1 to 6 or 7. A 1 per cent solution of antipyrine 
usually stopped the heart at once; one-half per cent solutions de- 
creased the rate quite markedly, but this effect was far more pro- 
nounced immediately after the introduction of the drug. Later the 
heart apparently became accustomed to the poisonous effects and 
little or no further slowing resulted, while in some cases actual increase 
in rate was observed after the primary slowing, a phenomenon which 
was also present after acetanilide, but less frequently. Solutions of 
0.8 per cent were generally found to be strong enough to cause marked 
changes and only occasionally stop the heart within a short time. 
This latter reaction appeared so erratically, however, that no conclu- 
sions could be drawn from the results obtained. In one case the 
heart might continue to beat for a half hour or more after the primary 
slowing with absolutely no further changes in rate. In other instances 
in experiments carried out in exactly the same manner, the heart 
would stop as soon as the drug reached it, a variability in action 
which seems to be somewhat more marked with this drug than with 
acetanilide. The changes in output were also similarly irregular, so 
that any conclusions were necessarily indefinite. 
The addition of caffeine citrate to an antipyrine solution caused no 
material change in the course of the poisoning, especially in regard 
to the efficiency of the heart. The primary slowing induced by 0.8 
per cent solutions of antipyrine was not prevented, the experiments 
indicating on the other hand that the slowing was greater from the 
combined action of the two drugs than from antipyrine alone. This 
represents the general result from a large number of experiments, 
but exceptions occasionally occurred. 
c^According to Cushny, Pharmacology and Therapeutics, 1906, p. 371, antipyrine is 
more toxic than phenacetine and less toxic tha.i acetanilide. 
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