1905.] Pharmacology of Indacomtine and Bikhaconitine. 
481 
Repeated Administration of Bikhaconitine at Stated Intervals to Rabbits. 
Effect on Temperature and Respiration. 

| Fraction of 
Total 



Greatest 
he ail eae How | PrOPOF- | fall of Subsequent course Note on 
iL. bedy peated. often. Fs ihe ree of temperature. respiration. 
: ure. 
weight. lethal. 
mins. a 
2 45 7 11 1 | Greatest reduction | Respiration _varies 
after second injec-| through 30 per 1’ 
tion. only. 
; 60 6 1°0 0°8 Greatest after second 
injection. 
+ 45 8 2 0 3°5 Greatest after fifth | Respiration remains 
injection. slow, 34 to 48 per 1’ 
during prevalence 
of low temperature. 
ss 60 6 1°5 1°2 
3 45 2 1°0 3 °2 Greatest after second. | Active dyspnea in- 
A third would have} duced. 
been fatal. 
He 90 3 1°5 2°9 Greatest after second | Respiration slowed 
injection. by 30. 
- 120 2 1:0 17 Greatest after second. 
5 180 2 1°0 Lea Greatest after second. | Respiration much 
The two falls are| slowed after each 
equal in extent. injection. 
65 240 2 1:0 1°3 Greatest fall after | Falls to one-half pre- 
first injection. existing rhythm 
after each injection. 

4. When such a proportion as one-quarter of the lethal is administered 
every 45’, or one-half of the lethal every 45, 60 or 90’, there is a decided 
summation of effect, and a further, often considerable reduction of temperature 
ensues upon readministration, so that in the former case the maximal fall 
does not occur until after the fifth administration. 
When a third administration of the half lethal dose of indaconitine is made 
at intervals of 45’, a lethal issue may occur, though this is exceptional, but 
the third dose of bikhaconitine so administered is lethal. 
5. As between bikhaconitine and indaconitine, it is further observable that 
the respiration accelerates less rapidly after the repetition of the former than 
when the latter is given, and to this may frequently be ascribed the greater 
accession to the fall of temperature after bikhaconitine. It appears that as a 
result of greater summation of effect produced by bikhaconitine, when doses 
larger than one-sixth of the lethal are administered, the action of the alkaloid 
becomes relatively greater than that of indaconitine. The toxicity of 
bikhaconitine is upon repetition of such doses, greater with regard to ind- 
aconitine than the relationship of the unit lethal dose, viz.,0°0000875 gramme 
to 000012 per kilogramme, would indicate. 
2K 2 
