THE PHARMACOLOGICAL ACTION OF HARMALINE. 271 



The animals (rabbits) were anaesthetised as for blood- pressure experiments, and 

 kept during the experiment in a bath of saline solution at 39° C, just enough of the 

 body being submerged to ensure that the uterus was never exposed to the air. The 

 abdomen was then opened in the middle line, and the uterus, isolated from the 

 surrounding viscera, was connected with a, lever writing on a slowly revolving drum. 



Experiment 37 (fig. 17). — Rabbit, 2100 grammes, non-pregnant. From 2.30 p.m. 

 there were slight spontaneous contractions of the uterus, just sufficient to move the 

 lever perceptibly. At 3.5 a dose of O'OOl gramme per kilogramme was given by the 

 jugular vein (see fig. 17). This brought on almost immediately a very powerful tetanic 

 contraction of the uterus lasting for about seven minutes, after which uterine con- 

 tractions again remained in abeyance. At 3.25 a second injection was given of 0*0005 

 gramme per kilogramme, which produced a similar tetanic contraction lasting for four 

 minutes. 



This experiment shows that harmaline, in doses which previous experiments have 

 shown to be the smallest to affect blood pressure, exerts a powerful action on the uterus 

 in the direction of inducing vigorous and sustained tetanic contraction. This fact 

 sufficiently explains the clinical observation that harmaline may cause abortion. It is 

 an effect which is also, but less powerfully, produced by quinine. 



General Summary. 



The minimum lethal dose of harmaline hydrochloride by subcutaneous injection is 

 for frogs 0*25 gramme per kilogramme, and for mammals (guinea-pig, rabbit, rat, and 

 cat) about O'l gramme per kilogramme. 



In frogs, lethal doses of harmaline paralyse the mid-brain and medulla oblongata, 

 and, at a much later period, the spinal cord. Abolition of reflex excitability occurs 

 before arrest of the heart, and before paralysis of the voluntary muscles. 



In mammals, large doses of harmaline cause epileptiform convulsions varying 

 somewhat in character in different animals. The convulsions are due to an action 

 on the cerebrum, probably especially affecting the cortex. Lethal doses paralyse the 

 spinal cord also in mammals, and, as in the case of frogs, this occurs at a later stage 

 than the action on the brain. 



The conductivity of nerve is impaired only by prolonged direct application of 

 strong solutions of harmaline, and the motor nerve-ends are slightly, if at all, affected 

 by this alkaloid. On the other hand, harmaline in comparatively weak solutions 

 causes rigor and excitability of voluntary muscle. 



When perfused through the frog's heart, strong solutions of harmaline cause almost 

 immediate systolic arrest of the heart ; weaker solutions cause slowing of the heart and 

 diminution of systolic contraction, and arrest of the heart, when it occurs, is in the 

 diastolic position. The latter kind of action is the only one which is observed in frogs 

 or mammals after subcutaneous administration of harmaline. 



