556 ANNALS NEW YORK ACADEMY OF SCIENCES 



that only a very small segment of nerve was exposed. It was, thus, 

 impossible adequately to wash the nerve, so as to preclude the possi- 

 bility of mechanical transfer of sufficient diisopropyl-fluorophosphate 

 to inactivate cholinesterase during the preparation of the nerve for 

 enzymatic studies. For this reason, a series of experiments was per- 

 formed in which a large dose of diisopropyl-fluorophosphate was in 

 jected into the ventral lymph sac of frogs and allowed to reach the 

 nerve, by way of the circulation. After a suitable interval, the nerves 

 were dissected and their transmission characteristics studied and com- 

 pared with control frogs. Following this, the cholinesterase content of 

 the control and experimental nerves was studied. Despite the fact 

 that the nerves of the experimental frogs were completely devoid of 

 cholinesterase, the transmission of the nerve impulse, as determined by 

 the characteristics of the action potential, in response to single and 

 repetitive stimuli, was unaffected. This finding casts serious doubt 

 on the role of acetylcholine as a de-polarizer, in the processes of con- 

 duction along the axon. 



Loewi, in his recent review, quotes Dale as having once remarked 

 that it was unreasonable to suppose that nature would provide for the 

 liberation in the ganglion of acetylcholine, the most powerful stimulant 

 of ganglionic cells, for the sole purpose of fooling physiologists. What, 

 then, is the function of cholinesterase in nerve fibers, which Nachman- 

 sohn and his co-workers have shown so conclusively to be concen- 

 trated at the surface, rather than in the axoplasm? The answer is not 

 yet forthcoming. However, in a drug like fluorophosphate, it is possi- 

 ble, by localized injection, to reduce the concentration of cholinesterase 

 in a chosen tissue to negligible amounts. Thus, we have a research tool 

 which may provide the answer to these basic problems. 



The third agent will be discussed only very briefly. It shares with 

 diisopropyl-fluorophosphate the ability irreversibly to inactivate 

 cholinesterase. It differs from diisopropyl-fluorophosphate in pos- 

 sessing a more outstanding action on the nervous system. Certain spe- 

 cies, in particular cats and dogs, exhibit severe convulsions, which have 

 their onset within a few minutes after the intravenous injection of the 

 drug and which persist until death. The fact that an anticholinesterase 

 agent possesses such extreme convulsant action could possibly be 

 attributed to coincidence. However, there is one finding which points 

 to an intimate relationship between convulsions and the chemical 

 mediation of central synaptic transmission. If the animals receive 

 a therapeutic dose of atropine, before the administration of this anti- 

 cholinesterase, no convulsions are observed, and complete protection 



