480 Prof. J. T. Cash and Dr. W. R. Dunstan. [May 24, 
animal is quiet and does not feed for a time. The variation in rectal 
temperature is not more than 1°C., a slight rise may or may not precede 
the fall. 
0000065 gramme per kilogramme.—The respiratory changes noted above 
are accentuated. Free salivation accompanied by chewing and retching 
movements, some paresis, especially of the hind legs, pupillary dilatation, and 
decline of temperature by 1:5 to 2° are observed. Recovery takes place in 
two hours. 
(°00008.—As the lethal proportion is approached all the symptoms are 
exaggerated. After transitory acceleration, there is respiratory slowing to 
one-quarter or one-fifth of the original. The respiration is for a time 
dyspneeal, the thorax expands but imperfectly, a prolonged pause in inspiration 
is usual. Respiration may become strident, and when this is the case 
dyspnceal spasms may occur. The pupilsare dilated. Paresis is considerable, 
the body becoming limp, this condition extending in degree to the sphincter 
ani. The fall of temperature amounts from 2 to 3° C., and if the body is not 
kept covered or exposed to warmth, a reduction of many degrees more is 
probable and death may result. On one occasion even with such precautions 
death resulted after a dose of this proportion. Recoveries, however, occur up 
to 00000875 gramme per kilogramme. 
0:00001.—This proportion is distinctly hyperlethal, death taking place in 
about 40’ and being primarily due to respiratory failure. It is preceded by 
dyspneeal convulsions. 
The lethal dose has been determined at 00000875 gramme per kilogramme. 
On one occasion only has a slightly larger proportion been recovered from 
(000009). 
From the tables of the effect of readministration of indaconitine and 
bikhaconitine respectively, as well as from experimental records which are not 
tabulated, the following points may be indicated :— 
1. For both alkaloids there is a marked tolerance when the dose is one- 
sixth of the lethal administered every 45 or 60’, or even of one-quarter when 
repetition is not more frequent than hourly. 
2. The greatest reduction after such administrations is after the second 
dose, and thereafter the temperature rises, though showing trifling checks 
when subsequent administrations are in progress. 
3. After smaller, as well as after larger doses, it is peculiarly in those cases 
in which respiration remains depressed that the relatively late occurrence of 
the maximum fall of temperature is to be looked for. In fact it may be 
predicted that the temperature will continue to fall, or at least, fail to rise, so 
long as respiration remains in the region of 30 to 35 per minute. 
