254 DR JAMES A. GUNN ON 



that the convulsions do not occur in an animal anaesthetised by ether or chloroform. 

 Apart from negative evidence, the epileptiform character of the convulsions points to 

 the brain as the seat of their origin. It is, moreover, probable that they are due 

 mainly to an exciting action on the cerebral cortex. The occurrence in cats of 

 symptoms apparently due to hallucinations suggests an action on the cerebral cortex. 

 Further, if the convulsions were due to an action on the lower part of the brain, they 

 would probably occur in frogs, as in the case of the convulsions produced by 

 picrotoxin. 



Tremors or convulsions are not produced in rabbits by doses less than 0"02 gramme 

 per kilogramme, i.e. one-fifth of the minimum lethal dose ; in the guinea-pig, tremors 

 occur after doses of above O'Ol gramme per kilogramme. 



In none of my experiments were the convulsions observed to be fatal, probably 

 because their clonic nature does not seriously interfere with respiration. 



After a period, which varies with animal used and the dose given, the convulsions 

 pass off, and in the case of smaller doses recovery ensues. In the case of larger doses 

 the convulsions diminish in severity and are succeeded by a stage of exhaustion and, it 

 may be, of complete motor paralysis, which may endure for some considerable time 

 before failure of the heart or respiration. When this stage of motor paralysis super- 

 venes, the symptoms referable to the central nervous system approximate closely to 

 those described in frogs, and are probably due to like causes. There is possibly an 

 increased excitability of the spinal reflexes in the early stages of poisoning in mammals 

 as in frogs, but of this it is difficult to be certain. However, it is clear that the 

 ultimate effect on the spinal cord, that of paralysis, is the same in mammals as in frogs. 

 This is well seen in Experiment 25 described above, where the spinal reflexes were 

 abolished some time before death, while the fact that the excitability of the peripheral 

 neuromuscular mechanism was unimpaired even some minutes after death showed that 

 this effect was central in origin. Owing to this paralysis of the spinal cord, the 

 terminal phenomena of asphyxia are unattended by convulsions. 



Though convulsions, due to an action on the cerebrum, may occur under certain 

 circumstances also with quinine, they are more typical of some of the other cinchona 

 alkaloids, e.g. cinchonamin. Harmaline and quinine are, however, alike in producing, 

 in large doses, diminution of excitability of the spinal cord in mammals. 



(b) Nerve. 



To investigate the action of harmaline on nerve structure, the following method 

 was employed. The muscle response was taken as an index of the condition of the 

 nerve. The gastrocnemius muscle of the frog was used, with the sciatic nerve carefully 

 removed leaving a small part of the spinal column attached. Two pairs of electrodes, 

 proximal and distal, were used to stimulate the nerve, and a small part of the nerve 

 between the proximal and distal electrodes was painted with a solution of harmaline. 



