246 DR JAMES A. GUNN ON 



with them salts which have a yellow colour and bitter taste. Harmaline hydrochloride 

 (C 13 H U N 2 0, HC1, 2H 2 0) forms long, fine yellow needles, easily soluble in water and in 

 alcohol. Dilute solutions of harmaline exhibit a green fluorescence.* 



The only observations hitherto made to determine experimentally the general action 

 of harmaline were those of Tappeiner in ] 8 9 5 . t His experiments were concerned 

 chiefly with symptoms produced in frogs and mammals. 



In frogs he found that harmaline produces paralysis of voluntary movement. 

 Reflex excitability remains after loss of voluntary motion, and even until arrest of the 

 heart and respiration ; after its complete paralysis, nerve and muscle are quite excitable. 

 No convulsions were observed. 



In mammals he found that harmaline produces motor disturbances, convulsions 

 followed by paralysis. Consciousness is retained during the convulsions, but the 

 sensitiveness to pain is reduced throughout the poisoning. Respiration is accelerated, 

 and the temperature slightly raised. He found the minimum lethal dose to be O'll 

 gramme per kilogramme, death being due to the arrest of respiration, which occurs 

 suddenly without any previous considerable reduction in frequency. 



From two kymograph experiments on rabbits, he concluded that the blood pressure 

 is at first considerably raised, especially during the convulsions. This rise is due to 

 stimulation of the vasomotor centre, since the heart's action did not appear to be 

 increased. Subsequently the blood pressure falls, owing to paralysis of the vasomotor 

 centre and increased weakness of the heart. 



He summed up as follows : " If we judge by the most apparent symptoms of 

 poisoning — the convulsions — which seem to be direct, as they are due to disturbance 

 neither of the respiration nor of the circulation, we can until further notice reckon 

 harmaline and harmine as convulsive poisons, and, in so far as death is due to arrest of 

 the respiration, also as respiratory poisons. This investigation gives no basis for its 

 therapeutic uses." 



In 1899 Oscar RaabJ investigated the action on Infusoria of several substances 

 which form fluorescent solutions, e.g. acridin, phosphine, quinine, and eosine. He 

 found that all of these are much more toxic to Paramcecium caudatum in light than 

 in darkness, those light rays which most excite fluorescence being especially powerful 

 in increasing the toxicity. In 1903 he extended these investigations to include 

 harmaline, § and found that a solution of 1 in 20,000 of harmaline kills paramcecia in 

 8 to 20 minutes, the presence or absence of light having no effect on the toxicity. 

 Nor does the light effect come into play with 1 in 40,000 ; but when exposed to a 

 solution of harmaline hydrochloride of 1 in 200,000, paramcecia remain quite healthy 

 in the dark for 20 hours, while in the light they die in 1 to 3 hours. Exposure to 

 light has by itself no injurious action on paramcecia. 



* Husbmann, Die Pflanzenstoffe, 1871, p. 76. 



t Archivfur exper. Pathol, u. Pharmakologie, Bd. xxxv., 1895, p. 69. 



1 Zeitschrift fur Biologie, Bd. xxxix., 1899, p. 524. § Ibid., Bd. xliv., 1903, p. 16. 



