550 ANNALS NEW YORK ACADEMY OF SCIENCES 



be classified in such general terms as local and general anesthetics, 

 analgesics, central stimulants, blocking agents, etc. For the purpose 

 of understanding the therapeutic application of drugs modifying 

 nervous activity, such information may be adequate. However, from 

 the standpoint of the contributions that drugs can make toward the 

 solution of basic problems in neurophysiology, our understanding of 

 their mechanism of action is as yet inadequate. 



Drugs have proved to be invaluable tools in many fields of biological 

 and medical research, a statement which the neurophysiologist would 

 be the last to deny. Their value is readily appreciated, when one con- 

 siders one of the few basic and general statements which can be made 

 concerning the fundamental mechanism of action of drugs: namely, 

 that drugs cannot impart new functions to cells or tissues, but can 

 only modify, i.e., stimulate, depress, or block, functions which are the 

 fundamental properties of that cell or tissue. Thus, when a drug pro- 

 duces general or local anesthesia, has a convulsant action, blocks 

 synaptic transmission, stimulates chemoreceptors, or affects nervous 

 activity in any of a variety of ways, no matter how extreme the re- 

 sponse, the assurance is justified, until an exception to the general rule 

 can be proved, that the drug in question has modified a normal cellular 

 function. 



Examples of how chemical agents, foreign to the body, have con- 

 tributed to physiological concepts are numerous. Indeed, through 

 these the subject matter of neurophysiology has been enriched. 

 Surely, it cannot be mere coincidence that so many basic contributions 

 to the concept of the chemical transmission of the nerve impulse had 

 their origin in pharmacological laboratories? Rather, the knowledge 

 that chemical agents could mimic, in end-organs, the effect of nerve 

 stimulation served as the basic stimulus for the search for evidence of 

 chemical mediation. Is it not possible that, in some drug, still inade- 

 quately explored by the neurophysiologist, lies the answer to a basic 

 neurophysiological problem? As a possible example, let us consider 

 the local anesthetics. The local anesthetic action of cocaine was first 

 demonstrated in 1884. This type of action has been shown to be 

 exhibited by a variety of chemical structures, but the tertiary amino 

 esters of benzoic acid and para-amino benzoic acid, as a group, are 

 capable of blocking transmission. These compounds show no respect 

 for any classification of nerves, but block cholinergic and adrenergic, 

 sensory and motor fibers in an indiscriminate manner, which points 

 to a basic action on a fundamental mechanism of transmission, shared 

 by all nerves. Is it nnt reasonable to suppose that, by inquiring more 



