96 THE PHARMACOLOGICAL ACTION OF HARMINE. 
spinal cord. Abolition of reflex excitability occurs before arrest of the heart, and 
before paralysis of the voluntary muscles. In mammals large doses cause epileptiform 
convulsions, cerebral in origin. If the dose be non-lethal these are soon recovered 
from ; if the dose be lethal, they give place to a condition of paralysis of the central 
nervous system, which endures for a short time before death. 
Harmine produces rigor and inexcitability of an isolated muscle, but, even with 
lethal doses, the concentration of harmine in the blood is not sufficient to render this 
action of importance in the general effects of this alkaloid. 
Strong solutions of harmine perfused through the frog’s heart slow the heart and 
arrest it in a position of almost complete diastole ; weaker solutions slow the heart and 
diminish the completeness of systolic contraction. The effects are due to an action 
on the cardiac muscle. 
Harmine has a slight peripheral constricting action on the frog’s blood-vessels. 
In mammals, harmine, in doses which have any marked effect on blood pressure, 
produces a fall of blood pressure due chiefly to slowing, or, in the case of large doses, 
to slowing and weakening, of the heart’s contractions. Cardiac failure is the chief 
cause of death from harmine poisoning. 
Sublethal doses of harmine stimulate respiration ; lethal doses paralyse respiration, 
partly from a direct action on the respiratory centre and partly as a consequence of 
circulatory failure. ; 
Like many convulsant poisons, harmine in large doses produces a fall of temperature 
in mammals. Even in small doses it stimulates the contractions and augments the 
tone of uterine muscle. 
CoMPARISON OF THE AcTIONS oF HaRMINE AND HARMALINE. 
The pharmacological actions of harmine resemble very closely those of harmaline in 
so far as the symptoms produced in the intact animal and the effects produced on the 
various systems and on isolated tissues are qualitatively the same in the case of both 
alkaloids. For this reason the pharmacology of the former alkaloid has been discussed 
more briefly. Harmine is, however, only about half as toxic as harmaline ; and probably 
the chief reason for the relatively lower toxicity of harmine is that the primary stimulat- 
ing action on the central nervous system less readily gives place to paralysis, and 
hence respiratory paralysis plays a less important part in the production of its lethal 
effects than is the case with harmaline. 
As the alkaloids can easily be obtained from the seeds in a mixed form, whereas 
their separation from one another is, I understand, a difficult and tedious process, this 
close similarity in their pharmacological actions possesses this importance, that the 
mixed alkaloids would apparently be as effective therapeutically as either alkaloid 
alone, should a therapeutic use for them be found. 
