The Action of Yohimbine on Medullated Nerve 193 



Interruption of the rhythmical stimulation but for a second sufficed to 

 restore the conductivity of the nerve to its previous condition. 



Now, on the assumption that the degree of anaesthesia does not increase 

 during the short period of observation, this peculiar form of tetanus points 

 to a progressive lengthening of the refractory period due to the con- 

 tinuous activity of the nerve, and any change in the direction of 

 depression of function which is solely due to activity is fatigue. That the 

 gradual prolongation of the refractory period is not due to a temporary 

 and coincident deepening of the anaesthesia is sufficiently clear from the 

 consistent regularity with wliicli the effect occurs even when the anaesthesia 

 is passing off. 



Frohlicli's work, while establisliing the fact that nerve can be fatigued 

 — a fact of fundamental importance in regard to our views as to the nature 

 of the nerve impulse— serves at the same time to emphasise the high powers 

 of restitution possessed by the structure. Even when anaesthetised almost 

 to the point of complete absence of conductivity, the nerve still required to 

 be stimulated uninterruptedly in order to maintain the fatigued condition. 

 Interruption of the rhythmical stimulation for a fraction of a second left 

 time for an apparently complete recovery. , 



The anesthetic agents which were found by Wedensky and Frolich 

 to prolong the refractory period of nerve include most of the common 

 anaesthetics known to medicine (ether, chloroform, cocaine, phenol, etc.). In 

 spite of the chemical differences between these substances, the kind of 

 change produced in nerve by means of all of them seems to be virtually the 

 same. Further, this change corresponds identically with that caused both 

 by asphyxia (4) and by cooling (9), so that one can recognise a common 

 element in the action of all of these things. 



The present paper deals with the changes produced in nerve by means 

 of yohimbine. This substance, which is an alkaloid derived from the bark 

 of the Yohimbehe tree (10), was shown by Magnani in 1902 to be a local 

 anaesthetic (11). We have investigated its action on the sciatic nerve of 

 the frog, availing ourselves of the method of Wedensky— i.e. rapid 

 rhythmical stimulation, in order to show changes in conductivity. The 

 response of the attached gastrocnemius muscle was used as an index of 

 the condition of the nerve. 



The investigation has shown : — 



(1) That fatigue changes in nerve may be demonstrated more readily 

 by the application of this substance than by any method known to us. 



(2) Yohimbine seems to differ somewhat in action on nerve from other 

 anaesthetics. 



For our experiments we used a 2 per cent, solution of yoliimbine 

 lactate in Ringer's fluid, which we applied to the middle portion of the 

 dissected nerve. In order to keep the solution in contact with this part of 

 the nerve, strips of blotting-paper (usually about 3 centimetres long) 

 moistened with the solution were laid under and over the middle portion. 



