THE PHARMACOLOGICAL ACTION OF HARMALINE. 269 



and acceleration of the heart, followed by dilatation of the former and slowing and 

 weakening of the latter."* Harmaline differs from quinine in its blood-pressure effects 

 in that the preliminary rise of blood pressure is due only to contraction of the arterioles 

 and not to acceleration of the heart, while the fall of blood pressure produced by large 

 doses of harmaline is due, so far as my experiments have shown, only to cardiac 

 slowing and weakening, and not to dilatation of the arterioles. 



F. Action on Respiration. 



Lethal doses of harmaline paralyse respiration both in frogs and in mammals. 

 Since at the time of death in mammals faradic stimulation of the phrenic nerve causes 

 tetanus of the diaphragm with a normally minimum stimulus (see Experiment 25), it is 

 probable that respiratory failure is due to paralysis of the respiratory centre. 



Especially during the time that convulsions occur, the rate and vigour of the 

 respirations are often increased. In none of my blood-pressure experiments (when 

 convulsions were prevented by anaesthesia) was an increase in the rate or amplitude of 

 the respirations observed, such as was found by Tappeiner. 



In the case of slowly fatal doses, death is due to arrest of the respiration alone, and 

 the heart may continue beating as long as ten minutes after respiration has ceased. 

 With larger doses, however, the heart-beats and respirations fail about the same time ; 

 indeed, one or two respiratory gasps may occur after it is impossible to feel any cardiac 

 impacts. 



Tappeiner stated that arrest of the respiration comes on somewhat suddenly, not 

 being intimated by any previous considerable reduction in frequency. This is only 

 partly true in the case of rapidly fatal doses, where the toxic effect on the heart attains 

 greater prominence. In the case of smaller lethal doses, where heart failure does not so 

 materially contribute to the cause of death, there is a gradual and progressive 

 diminution in the rate of the respirations. 



G. Action on Temperature. 



Tappeiner stated that "the body temperature is rather heightened than lowered. 

 In one case in a rabbit it was 40'4° C. and in a dog 397° C. in the rectum." It is 

 unfortunate that he does not state with what doses or at what times after injection this 

 elevation of temperature occurred, and also what was the temperature before injection. 

 In the rabbit the normal temperature may be above 40 '4° C.t 



In my experiments I have not observed with any dose a definite rise of temperature, 

 while large doses invariably produce a fall of temperature, in regard to which action 

 harmaline resembles quinine. 



* Cushny, Textbook of Pharmacology, 3rd edit., p. 360. 



t Simpson and Galbkaith, Journal of Physiology, 1905, p. 230. 



TRANS. ROY. SOC. EDIN., VOL. XLVII. PART II. (NO. 11). 40 



