552 ANNALS NEW YORK ACADEMY OF SCIENCES 



scribed. They are conveniently labeled as convulsants, depressants, 

 etc., and sporadic attempts are made to localize their action, following 

 which, investigation is considered to be complete. I wish to take this 

 opportunity to present three new compounds which have come to the 

 attention of those who, during the past few years, have been workin:? 

 in the field of chemical warfare. These are highly toxic agents which 

 must, by definition, exert profound effects on basic cellular mechanisms. 

 As a result of the cooperative research program, associated with the war 

 effort, these compounds have received more fundamental study, in the 

 course of a few years, by groups with more divergent interest, than is 

 usually the case with better-known and more widely-employed drugs. 

 These three compounds have been selected for discussion from a large 

 group, because of the profound actions which they exert on the nervous 

 system. 



The first of these compounds is the sodium salt of fluoroacetic acid. 

 This agent has had an interesting history. It represents, in its prac- 

 tical applications, one of the many fruitful by-products of chemical 

 warfare research. Sodium fluoroacetate was screened by the Fish and 

 Wildlife Service and has proved to be by far the most outstanding of 

 all rodenticides. Now known as Compound 1080, it promises to be 

 an important agent in the control of the spread of disease and the eco- 

 nomic wastage caused by rodents. Yet the prediction is not unjustified 

 that the compound may prove to be of even more significant value as a 

 laboratory research tool, assuming equal importance, in this respect, 

 with the iodoacetates. 



Although the fluoroacetate ion resembles iodoacetate in structure, it 

 shares none of its chemical or physiological properties. However, both 

 halogenated acetates exert profound effects on cellular metabolism. 

 Highly provocative are the observations of Barron and co-workers,^ 

 that the oxidation of acetate by yeast, rat kidney suspensions, and 

 heart slices is inhibited by fluoroacetate. When pyruvate is used as 

 the oxidizable substrate, there is an accumulation of acetate, after the 

 addition of fluoroacetate, and the synthesis of carbohydrate from 

 pyruvate is completely inhibited. Barron has advanced the reasonable 

 hypothesis that fluoroacetate, because of its close structural relation- 

 ship to acetate, blocks, by competitive inhibition, enzyme systems con- 

 cerned with the utilization of acetate. 



When one considers the basic importance of acetate metabolism, it 

 is of extreme interest to inquire into the pharmacological actions of a 

 compound which, possibly, interferes with the utilization of this essen- 

 tial metabolite. These actions have been investigated by Chenoweth 



