90 



MARTIN G. LARRABEE AND PAUL HOROWICZ 



TABLE III 



Effects of metabolic inhibitors on nerve conduction and on synaptic 

 transmission in superior cervical ganglia excised from rats 



(Observations by N. A. Coulter and J. Dempsher) 



Inhibitor 



NaCN 



NaN 3 



Malonate 



Iodoacetate 



Iodoacetate 



2,4 dinitrophenol 



Reduced temperature. . 



Cone. 



12 mM 

 7 mM 



14 mM 

 0.1 mM 

 0.5 mM 

 0.22 mM 



13°C. 



Possible Site of Action 



Cytochrome oxidase 



Cytochrome oxidase 



Krebs' cycle 



Glycolysis 



Glycolysis 



Phosphorylation 



General 



* Heights of action potentials became constant at indicated levels during application of 

 inhibitor. 



This table reproduced from Larrabee and Bronk (1952). 



few experiments with cyanide. Thus none of these metabolic inhibitors pro- 

 duced a selective action comparable to that of pentobarbital, for example, 

 which completely blocked transmission through a ganglion in concentrations 

 causing no depression at all in the response of the preganglionic nerve. 



Conclusion 



In the foregoing discussion, we have touched on only a few of the types of 

 metabolic studies that have been made by other investigators in relation to 

 anesthetics. Innumerable such investigations, some on excised tissues and 

 others on tissues in situ, have revealed many significant effects and have led 

 to many interesting theories of anesthetic mechanisms. But as the story now 

 stands, real difficulties in deciphering causal relations in anesthetic action are 

 found in the experimental approaches which have been applied to the meta- 

 bolic aspects of the problem. 



In our own experiments, measurements of metabolism and tests with in- 

 hibitors have produced no compelling support for the metabolic hypothesis of 

 anesthetic action. Neither has this interesting and important theory been con- 

 troverted. In this connection it may be noted that a substance becomes classi- 

 fied as an anesthetic when it has been found on an entirely empirical basis to 

 produce a certain general category of effects in the intact organism. Therefore 

 it is possible that chemical agents, thus selected with attributes desirable for 

 inducing anesthesia, may all be ones which cause metabolic disturbances not 

 revealed in changes of oxygen uptake and not matched by any of the in- 

 hibitors listed in Table III. 



