THE PHARMACOLOGICAL ACTION OF HARMALINE. 249 



Harmaline resembles quinine in being relatively much more toxic to mammals 

 than to frogs. 



B, Symptoms produced by Harmaline. 



(a) In Frogs. 



The following experiment will serve to illustrate the symptoms produced by a 

 minimum-lethal dose of Harmaline. 



Experiment 5. — Rana temporaria, male, weight 38 grammes. At 11.27 a.m. the 

 throat respirations were 1 7 in ten seconds, deep and regular ; the cardiac impacts were 

 7 in ten seconds, fairly easily seen. Faradic stimulation of the skin of the right leg 

 with the secondary coil at 160 mm. elicited a slight kick of the same leg, and the 

 animal moved away if the stimulation was prolonged ; similar stimulation with the 

 coil at 140 mm. caused immediate extension of both legs. Stimulation of the skin over 

 the dorsal part of the spinal cord caused extension of the legs with the coil at 140 mm. 



At 11.50, 0'0095 gramme of harmaline hydrochloride dissolved in 0*8 c.c. of 

 Ringer's solution was injected into the dorsal lymph-sac. This was equivalent to 0'25 

 gramme per kilogramme. 



At 11.58 the pupils, which had been medium before injection, were more con- 

 tracted. The results of electrical stimulation were the same as before. There was 

 persistent contraction of the muscles running from the skin to the side of the urostyle. 



At 12.5 p.m. the respirations were 13 in ten seconds, and very feeble. The back 

 was rigid, and curved in a direction concave upwards, due to rigidity of the back 

 muscles. The frog jumped away when the skin of the leg was stimulated at 230 mm., 

 and turned immediately when placed on its back. 



At 12.14 the rate of the respirations had fallen to 9 in ten seconds. With the coil 

 at 160 mm., stimulation of the skin of the right leg caused extension of both legs, 

 while at 12.34 the coil required to be at 145 mm. to produce this effect. 



At 1.50 the pupils were contracted. An area of skin overlying the dorsal lymph- 

 sac was pale, contrasting markedly with the much darker colour of the skin of the 

 rest of the body. The respirations were only 3 in ten seconds, and consisted of very 

 feeble undulations of the anterior part of the floor of the mouth. The cardiac impacts 

 were 3 in ten seconds. The reflex excitability as determined by electrical stimulation 

 was unchanged. When the frog was laid on its back it made no effort to recover, but 

 when the foot was now stimulated the frog turned over with difficulty. The animal 

 jumped only if strongly stimulated, and when it alighted the hind limbs were not 

 drawn up with normal rapidity. 



At 2.25 the respirations had ceased, and the cardiac impacts were not visible, but 

 when the web of the foot was examined under the microscope the circulation was seen 

 to be active. At 3.15 the animal lay prone, with limbs extended. The conjunctival 

 and nose reflexes were active. 



