THE PHARMACOLOGICAL ACTION OF HARMALINE. 253 



to an action of harmaline on this part of the brain. However, the onset of inco- 

 ordination of movement, the loss of the power of jumping and of recovering the 

 normal posture when the animal is laid on its back, and the cessation of respiration — 

 occurring as these effects do at a time when the spinal reflexes and peripheral motor 

 mechanism are slightly, if at all, impaired — indicate that harmaline first paralyses the 

 functions of the mid brain and medulla oblongata. 



With regard to the spinal cord, a transient stnge of increased reflex excitability 

 usually occurs, after which spinal reflexes become less and less easily elicitable. The 

 voluntary muscles still readily respond to weak faradic stimulation of their nerves 

 when the abolition of reflex excitability first occurs, showing that the paralysis is one 

 involving the spinal cord. 



As is the case with many poisons, the power of transmission of impulses across the 

 spinal cord, e.g. from left to right leg, is lost much earlier than the power of 

 conducting impulses down the spinal cord, rendering it probable that the block in 

 conduction is due not to paralysis of the efferent nerve cells but to interference between 

 the afferent and efferent nerve cells of the cord. Loss of reflex excitability occurs 

 before arrest of the heart, if the heart be not exposed. 



Harmaline resembles quinine very closely in its action on the central nervous 

 system of the frog. Like harmaline, quinine in large doses paralyses the brain and 

 respiratory centre, and later the reflex excitability of the spinal cord after a pre- 

 liminary increase of excitability. In quinine poisoning too the heart continues to beat 

 after paralysis of the spinal cord. 



2. In Mammals. — Harmaline affects the central nervous system of mammals in a 

 manner different from the central nervous system of frogs, in so far as symptoms of 

 excitation are added to symptoms of paralysis. Convulsions do not occur in frogs, but 

 are the most conspicuous effects produced in mammals. 



In the cat these take the form of more or less violent convulsions of epileptiform 

 character, occurring at irregular intervals and separated by quiescent periods. In the 

 guinea-pig, clonic convulsions, less violent than those produced in the cat, and 

 resembling running movements, occur almost without respite. In the rabbit, con- 

 vulsive movements of an intermediate type are observed ; and in the rat, spasticity of 

 the limb muscles, with tremors and swaying of the head and body, is the most 

 characteristic appearance, though the kind of clonic convulsions described in the 

 guinea-pig occurs also in the rat. 



Certain facts in regard to these convulsions aid in the localisation of the site of 



their production. In the first place, they are not due to asphyxia, because they occur 



before there is any impairment of respiration or any appearance of cyanosis. In the 



second place, the convulsions are cerebral in origin and not spinal. They are quite 



different from the convulsions produced by strychnine, for example ; they are not 



evoked by any apparent external stimulus, opisthotonus is never seen, and the 



convulsions do not occur in frogs. Also it will be shown in kymograph experiments 

 TRANS, ROY. SOC. EDIN., VOL. XLVII. PART II. (NO. 11). 38 



