OILMAN: EFFECTS OF DRUOS ON NERVE ACTIVITY 557 



is afforded from what would, otherwise, be a lethal dose. Moreover, 

 if the agent is administered and the convulsions are allowed to progress 

 to their peak intensity, the intravenous injection of atropine stops 

 all convulsive activity within 30 seconds, and the animal appears nor- 

 mal, as soon as it recovers from its exhaustion. It should be empha- 

 sized that the doses of atropine that exert this anticon\^lsant action 

 are of a small magnitude and, in themselves, exert no demonstrable 

 central effects. No other central stimulant can be inhibited in this 

 manner. The effect of atropine, in blocking the convulsant action of 

 this anticholinesterase, is as dramatic and as complete as is the effect of 

 atropine in blocking the reception of post-ganglionic cholinergic im- 

 pulses by autonomic effector cells. It seems certain that, in this com- 

 pound, there is a research tool which can make a significant contribu- 

 tion to the fundamental problems of central synaptic transmission. 



During the past few years, the group of investigators at Edgewood 

 Arsenal has been engaged in a cooperative research effort, in which toxic 

 war gases or, in other words, highly active drugs, were the focal point of 

 their investigations. Their efforts were coordinated with extensive 

 programs of numerous academic groups. From the point of view of 

 the pharmacologist, this elaborate approach to the mechanism of drug 

 action has proved to be an illuminating experience. One cannot fail to 

 be impressed by the fact that, as the story of each agent unfolded, its 

 potential value toward the solution of fundamental problems in phy- 

 siology and biochemistry was more and more appreciated. 



I have departed from a routine discussion of the effects of drugs on 

 nervous activity, to present to you three new agents which have re- 

 sulted from this program. It may be predicted that, as research tools, 

 they will prove invaluable. If so, then the contention made earlier will 

 have been fulfilled: that, by tracing the actions of drugs to their cellular 

 mechanisms, basic physiological processes will be revealed. 



REFERENCES 



1. Barron, E. S, G., G. R. Bartlett, & G. Kalnitsky 

 1946. Fed. Proc. 5(11): 120. 



2. Chenoweth, M. B., & A. Gilman 

 1946. J. Pharm. Exp. Therap. 87; 90. 



3. Tepperman, J., & A. Mazur 

 Per.sonal Comiiunication. 



4. Comroe, J. H., Jr., J. Todd, G. Gammon, G. B. Koelle, & A. Gilman 

 1946. Fed. Proc. 5(11) : 172. 



5. Harvey, A. McG., B, F. Jones, S. Talbot, & D. Grob 



1946. Fed. Proc. 5(11): 182. 



6. Crescitelli, F. N., G. B. Koelle, & A. Gilman 



1946. J. Neurophysiol. 9:24. 



