362 Proceedings of Royal Society of Edinburgh. [sess. 
Small doses, or large doses given subcutaneously, always depress 
the cord as the first stage of their action. If, however, me thy 1- 
codeium sulphate in sufficient dose (2 centigrammes) be injected 
directly into the aorta (after protecting the motor nerves) we get 
tetanus at once without any preliminary depression of reflexes. 
Five centigrammes is the usual lethal dose for a frog. This is 
larger than the lethal dose of codeine, but smaller amounts of it 
than of codeine produce physiological action. It may therefore be 
regarded as much more powerful than codeine (in frogs). The 
reason of its lethal dose being so large probably is that the paralysis 
of the motor nerves prevents the tetanic spasms, and thus protects 
the frog from the exhaustion consequent on convulsions. 
Rabbits. — Crum Brown and Fraser found that methyl-codeium 
sulphate had no hypnotic effect on rabbits. This is hardly the 
case, however, although it is diminished to a very great extent. 
Thus the large dose of 1 decigramme had almost no action of any 
kind beyond causing slight quietude. 
When 0*2 grm. is given the narcotic action is well marked, and 
is accompanied by a certain degree of increased reflex. There 
seemed to be also some depression of the motor nerves which 
obscured the symptoms rather. 
Expt. 26. — Rabbit, 1170 grms. ; H., 28; R, 22 in 10 seconds. 
2.45. — 0*2 methyl-codeium sulphate subcutaneously. 
2.55. — Has lain down. 
3.0. — H., 32; R., 17. Vessels of ears very dilated. 
3.5. — Pupils small, chin on table, drowsy. 
3.10. — H., 29; R., 13. Ears same, pupils smaller, lies in any 
position in which it is placed. Slight touch of leg causes violent 
tetanic jerk of whole body. Quite sensitive to pain. 
3.16. — Lies in any position; corneal reflex very sluggish. 
3.30. — Has been lying as if deeply narcotised. Pays no atten- 
tion to slight stimuli. Increased reflex has quite passed off. H., 
29 ; R., 7. No sign of dyspnoea. 
3.45. — Rabbit made a great effort and sat up. Very drowsy and 
shaky. 
4.5. — H., 26; R., 12. Very drowsy. 
Next day. — Well. 
Larger doses cause death from paralysis of motor nerves. Thus 
