THE PHARMACOLOGICAL ACTION OF HARMINE., 87 
At 11.55 the conjunctival reflex was with difficulty elicitable. The thigh muscles 
and muscles of the right flank were stiff. The temperature was 96°4° C. 
At 12.9 the animal made no movements, apart from those of respiration which were 
feeble and irregular, the rate being about 9 in ten seconds. The heart beats were feeble, 
irregular, and infrequent. 
At 12.12 the respirations ceased. The thorax was opened, and at 12.13 the heart 
found to be beating very feebly. It ceased beating in the diastolic position at 12.15. 
The muscles round the seat of injection were rigid and inexcitable. The muscles of the 
fore limbs reacted to weak stimulation of their nerves, as also did the diaphragm to 
stimulation of the phrenic nerve. 
C. AcTion oN THE CENTRAL NERVOUS SYSTEM. 
(a) In Frogs.—'the description given of the symptoms produced by lethal doses of 
harmine in the frog has shown that the chief effects referable to an action on the central 
nervous system are loss of co-ordination and of the power of jumping, arrest of respira- 
tion, and paralysis of reflex excitability. Since these effects come on at a time 
when they cannot be accounted for by paralysis of the peripheral neuro-muscular 
mechanism, they indicate that harmine paralyses the mid-brain, medulla oblongata, 
and spinal cord. 
(b) In Mammals and Pigeons.—Epileptiform convulsions form the most conspicuous 
symptom produced by large doses of harmine in warm-blooded animals. They are 
clonic in nature and are usually intermittent, intervals of quiescence ensuing between 
the convulsions. They are generally aggravated by any voluntary movement. All the 
facts observed in regard to these convulsions, among which may be mentioned their 
clonic nature, their occurrence apart from any marked increase of spinal reflex excita- 
bility, and their absence in frogs, point to their being due to an exciting action on the 
cerebrum. 
In regard to this action of harmine on the cerebrum, it is of interest to observe that 
the minimum lethal dose per kilogramme for a series of animals is roughly in inverse 
proportion to the amount of grammes of brain per kilogramme of body weight in those 
animals. A somewhat similar relationship occurs with cocaine, which also produces 
cerebral convulsions. * 
The clonic convulsions produced by harmine are not directly fatal to the animal, as 
they do not markedly interfere with respirations. When the dose is lethal, the con- 
vulsions are followed for a short time before death by a condition of motor paralysis 
due to a depressing action on the central nervous system. If the dose be not lethal, the 
convulsions are usually entirely recovered from within one or two hours. 
* Dixon, Manual of Pharmacology, 1906, p. 145. 
