12 
Fr. Bennefeld® in 1881 undertook an investigation of the relative 
activity of tinctures of digitalis obtained from different parts of Ger- 
many. He first tried to compare them by means of their specific 
gravities and the amount of the dried residue, but his results, con- 
firming those of Schneider, 6 showed that such examinations were 
worthless. He then adopted the physiological method, employing 
rabbits as experimental animals. 
The tinctures were prepared for examination by evaporating 25 c. c. 
and drying the resulting residue to constant weight over sulphuric 
acid. The residue was digested on a water bath for fifteen minutes 
at a moderate temperature with 15 c. c. of distilled water, was then 
filtered as quickly as possible and brought to a volume of 20 c. c. 
Before injection it was heated to body temperature. 
The rabbits used were of the same age, weight, and resistance as 
far as possible. After inserting a cannula into a jugular vein, the 
modified tincture was injected at regular intervals in 0.5 c. c. doses 
until the animal died or the 20 c. c. was exhausted. 
His results showed that the minimum lethal dose for the eight 
tinctures varied from 3.36 to 15.97 c. c. of the residue solution per 
kilogram, body weight, while the time of death varied from eleven to 
fifty-four minutes. 
Frankel c adopted still another method to determine the compara- 
tive activity of different preparations of digitalis. Dogs weighing 
between 10 and 18 kilograms were curarized and the drug injected 
subcutaneously in doses not exceeding 10 c. c. His standard for 
comparison consisted in the amount which was necessary to produce 
the digitalis effect, viz, a decrease in the rate of the heart with an 
increase in the volume of the single beats. He also registered the blood 
pressure. 
He found marked differences between the various preparations in 
the amount necessary to bring about the desired effects, which he 
thought might be partly due to individual variations in the dogs and 
also possibly to the curara. The tincture was found to be very weak, 
while the acetum was the stronger preparation, but the active amounts 
of both acetum and infusion were quite variable. 
Laborde and Duquesnel d examined two samples of digitalien 
(Nativelle) as to their chemical purity and physiological activity, 
using for the latter purpose frogs and guinea pigs. 
The hearts of the frogs were exposed and the drugs injected in 
5-milligram doses, the effects being noted. With one preparation 
« Fr. Bennefeld, fiber Digitalis-Tincturen, Comparativ-experimentelle Unter- 
suchungen, Inaug. Dissert., Gottingen, 188L 
&von Schneider, Arch. d. Pharm., 1879, COXY, 412. 
c Frankel, Charite-Ann., Berl., 1881, YI, 207. 
d Laborde and Duquesnel, Comp. rend. hebd. des Seances et Mem. de la Soc. de 
Biol., 1884, XXXYI, 93. 
