336 Proceedings of Royal Society of Edinburgh. [sess. , 
marked narcosis preceding the tetanus, while 2 centigrms. might 
give tetanus almost at once. It is clearly a question of rapidity of 
absorption. 
With the smaller doses the tetanus is exactly like that of strych- 
nine ; hut with larger amounts there is great tendency to exhaus- 
tion, just as with morphine, so that soon no tetanic spasm can be 
induced, the frog responding to stimulation by a mere twitch. 
This condition depends partly on depression of the cord and partly 
on depression of motor nerves. When the codeine is injected 
directly into the aorta tetanus occurs at once. Thus, 
Expt. 6. — Frog pithed ; body ligatured, with exception of lumbar 
nerves. 
12.22. — 0 - 005 grm. codeine in \ cub. cent, water and acetic 
acid (q.s.) per aortam. 
12.23. — Violent tetanus. 
12.28. — Tetanus is becoming less violent, hut is still marked. 
12.45. — Is now a good deal exhausted, hut still gives a violent 
jerk on stimulation. 
1.0. — FTo response on stimulation. The cord is quite exhausted. 
The brachial nerves (unprotected) are quite excitable at 180 mm., 
the sciatic nerves (protected) also excitable at 180 mm. 
Experiments made ia the same way with 1, 2, 3, and 5 centigrms. 
gave similar results, but exhaustion ensued more rapidly, and, 
especially with the larger doses, the motor nerves were completely 
paralysed, or very much depressed in excitability. When small 
doses such as |~2 milligrms. are administered by the aorta, there 
occurs a stage of depression, followed by an increase of reflexes, 
just as in the case of morphine. 
With regard, therefore, to the action of codeine on the cord, we 
find (as with morphine) that small doses depress its reflex and con- 
ducting power, while larger ones cause tetanus. If a large dose he 
thrown at once into the substance of the spinal cord by injecting 
it directly into the aorta, then no preliminary narcotic stage occurs, 
but an increase of reflexes from the very first. 
The action of codeine on the motor nerves in frogs is very 
distinct. When the codeine is injected directly into the vessels it 
occurs very rapidly, hut if a large dose (about 5 centigrms.) be 
given subcutaneously, paralysis or very marked depression occurs 
