THE PHARMACOLOGICAL ACTION OF HARMALINE. 255 



A comparison was made, before and after the application of harmaline, of the muscle 

 response evoked by proximal and distal stimulations. 



It was found that nerve is very resistant to harmaline : even so strong a solution as 

 2 per cent, of harmaline hydrochloride impairs the conductivity only after several 

 hours' application. This feeble action on nerve presents a marked contrast to the 

 unusually toxic effect which harmaline exerts on striped muscle. 



As in the case of the nerve trunks, so the motor nerve terminals are slightly if at all 

 affected by harmaline. Thus in Experiment 5, in the course of impairment of the 

 peripheral neuromuscular mechanism, stimulation of the sciatic nerve of the frog caused 

 contraction of the gastrocnemius with the coil at 295 mm., while direct stimulation of 

 the muscle required a strength of 50 mm. This relation of excitability appears to show 

 that the peripheral paralysis, which occurs late in the course of poisoning, is due to 

 paralysis of the muscle, the nerve and nerve-ends being slightly if at all affected. This 

 opinion was confirmed by investigating the action of harmaline on the nerve-muscle by 

 Claude Bernard's method, when it was found that diminution in excitability of muscle 

 when stimulated through its nerve occurred only when there was a corresponding 

 decrease in the excitability of the muscle to direct stimulation. 



D. Action on Skeletal Muscle. 



It has been shown that, after injection of harmaline, rigor and loss of excitability 

 occur in those muscles to which the injected solution obtains more direct access. This 

 produces an appearance of opisthotonos when the injection is made into the dorsal lymph- 

 sac, of emprosthotonos when the injection is made under the skin of the abdomen. 

 Arrangements were made to test further this action of harmaline by keeping a muscle 

 directly in contact with solutions of varying strengths of the alkaloid. A modified 

 Wild's method was employed ; and when the muscles were stimulated, the current from 

 the secondary coil passed simultaneously through both muscles. Tracings were taken 

 on a slowly revolving drum. 



Experiment 26 (figs. 1 and 2). — Strength of solution, 1 in 500. Normal twitches 

 resulting from stimulation of the muscles with break shocks are shown at 11.40 (fig. 1). 

 At 11.45, Ringer's solution was withdrawn from the upper tube, and a solution of 

 harmaline hydrochloride (1 in 500 of Ringer's solution) was substituted. Almost 

 immediately this caused the muscle to pass into rigor. This proceeded so rapidly that 

 in five minutes this muscle had raised the lever above the level of the summit of 

 a single twitch. 



At 11.58, thirteen minutes after exposure to harmaline, the upper muscle ceased to 

 respond to stimulation, whereas the control muscle contracted as before (fig. 2). 



This strength of solution therefore very soon brings on rigor with loss of 

 excitability of the muscle. 



Rigor of frog's muscle is produced by solutions of harmaline even so dilute as 1 in 



