14 PHYSIOLOGICAL ACTION OF DAPHNANDRA REPANDULA ; 
This extract is very hard and soluble to any extent in water. 
It is very convenient, as being free from gum and resin, for use in 
hypodermic syringes. A grain is a fatal dose for frogs; one to 
ten grains for warm-blooded animals. 
To prepare the alkaloids, exhaust the bark by repeated treat- 
ment with hot water, precipitate with tannic acid, decompose in 
the usual way. 
Separate the different alkaloids as follows :—Boil in water in 
which medium the most poisonous one only is soluble, treat the 
residue with ether which dissolves another, leaving a third which 
is soluble in alcohol and chloroform, in which media the other 
two are also soluble. They are all colourless when pure crystal- 
line, differing from each other in appearance; their salts are 
crystalline and bitter. The active alkaloid is insoluble in ether, 
benzene, and turpentine, slightly soluble in chloroform and amyl- 
alcohol, soluble in alcohol and water. 
The frogs made use of in this investigation were the large green 
tree frog (Hyla czerulea). 
The dust given off during pulverisation of the bark causes 
sneezing and secretion from the nasal mucuous membrane. Frogs 
after having had Daphnandra extract injected into a lymph-sac 
remain very still. There is irregularity and difficulty of breathing, 
soon ending in paralysis of respiration, loss of reflex function, and 
in several hours the heart stops in systole. There is slowing of 
the circulation and dilatation of the veins, sometimes constriction 
of the arterioles, oftener no change whatever in the calibre as 
ascertained by micrometer measurements in the web of frogs 
slightly under the influence cf curara. 
The slowing of the heart seems to be caused by lengthening of 
the systole. There is intermittancy, more auricular than ventricular 
pulsations, less blood passing through the heart, the heart in con- 
sequence appears much smaller ; finally no ventricular beats, the 
ventricle remaining firmly contracted, the auricles and sinus beat 
for some time longer and stop generally distended with blood. 
Atropine does not hinder the action of Daphnandra in slowing 
and stopping the frog’s heart. 
Daphnandra slows the frog’s heart whether the vagi are intact or 
previously cut ; whether administered through the circulation or 
topically applied to the heart in situ or after removal from the 
body, and even when the sinus venosus is severed from the heart. 
Daphnandra seems therefore to chiefly affect the motor ganglia of 
the heart. 
