10 
feine in itself was useful in certain forms of headache, and it appeared 
in several formulae combined with the bromides a number ot years 
before the introduction of antipyrine and acetanilide. The natural 
inference, therefore, is that it was a direct transfer of caffeine from 
the old to the new type of headache remedies. The other explanation 
of its presence is to be found in the literature relating to the treat- 
ment of cases of acetanilide poisoning. Lepine “ seems to have first 
suggested caffeine as an antidote, having reported that the cyanosis 
of acetanilide poisoning disappeared after large doses of this drug. 
In 1889 Mahnert^ suggested that the excitants be used, and in treat- 
ing three cases made use of ether injections, wine,* and powdered 
caffeine, the latter being especially recommended by him. Hartge^^ 
treated a case of poisoning with coffee and brandy and later with 
camphor and ether injections. Falk ^ used caffeine, but thought that 
alcohol was distinctly contraindicated, owing to the increased solu- 
bility of acetanilide in this menstruum and therefore its more rapid 
absorption. Such a course of treatment for acetanilide poisoning 
might easily have suggested the addition of one of the above drugs to 
acetanilide mixtures with the idea that poisoning would be prevented. 
Whether caffeine was introduced into them as an active agent in the 
cure of headache or merely to give an additional safety to a drug 
with known poisonous properties it is of course impossible to say, and 
both factors may have played some part. At any rate caffeine thus 
introduced has been almost invariably a constituent of all prescrip- 
tions or proprietary formulae containing acetanilide. 
The generally prevailing idea at the present time is that caffeine 
is added to prevent the deleterious effects of the coal-tar drugs upon 
the heart,^ although this does not seem to have been the original 
reason for its administration. No direct observations concerning 
its antidotal value seem to have been made, but on purely theoretical 
grounds it would apparently be useful as a stimulant to the respira- 
tory center, which becomes markedly embarassed from the formation 
of methsemoglobin and to a lesser degree to the heart. It does not 
seem probable that it would have any special influence upon the 
cyanosis unless indirectly through increased respiratory activity. 
The combination of alkali carbonates with acetanilide also became 
popular about 1890, but the reason for their presence in acetanilide 
« Lepine, Rev. de med. Par., 1887, VII, 531. 
&Mahnert, Memorabilien, Heilbr., 1889, XXXIV, 321. 
cHartge, St. Petersb. med. Wchnschr., 1890, VII, 69. 
<^Falk, Therap. Monatsh., 1890, IV, 257. 
^McFarline, Canad. Pharm, Jour., Toronto, 1906, XXXIX, 360, says in speaking 
of headache powders: “It will be noted that in most cases the depressant effect 
upon the heart is sought to be counteracted by the addition of caffeine, bicarbonate 
of soda, or other drugs of like character.” 
