PHARMACOLOGY 



Because of disagreement concerning the concentration of various 

 narcotic agents in brain tissue, at varying depths of anesthesia, evalua- 

 tion of the observations of Quastel and his co-workers is not a simple 

 matter. Fuhrman and Field (8) concluded that, during anesthesia, 

 the concentration of certain narcotic agents in the brain is less than 

 one-fourth that required for the inhibition of glucose oxidation by 

 brain tissue in vitro; however, their conclusions do not appear to have 

 been based on adequate analytical data. Further studies will evi- 

 dently be required to establish whether those concentrations of narcotic 

 agents which produce anesthesia in vivo inhibit to an appropriate degree 

 any of the enzyme systems that are required for the normal functions 

 of the brain. The effect of narcotic agents on the functions of other 

 tissues must also be considered, since it has been shown (22) that 

 certain enzyme systems of skeletal muscle are inhibited by chlorobutanol 

 to the same degree as are comparable systems of brain. However, the 

 functional activity of muscle does not appear to be inhibited by those 

 concentrations of chlorobutanol attained during anesthesia. 



Even if it were found that the concentration of narcotic agents 

 required to inhibit certain enzyme systems, or the over-all respiration, 

 in vitro, is significantly greater than the concentration attained during 

 anesthesia, a reaction more specifically concerned with the functional 

 integrity of the nervous system may be found that is inhibited by lower 

 concentrations. In favor of the theory that narcosis involves a more 

 general depression of energy-transferring mechanisms in nervous 

 tissue, however, is the wide variety of chemical structures, usually 

 lipid-soluble, which produce a reversible narcotic effect on many types 

 of cells. The importance of further study in this field of investigation 

 is clearly indicated. 



" Seevers and Shideman (33) have made rather extensive studies 



of morphine in an attempt to place its action on a biochemical basis. 

 In confirmation of the findings of Quastel and Wheatley (26) it was 

 shown that the drug in high concentration (0.12%) inhibits the oxygen 

 consumption, in vitro, of the cerebral tissues of rats, when certain 

 substrates, particularly lactate, are added. In the absence of added 

 substrates no effect was observed. Various mammalian dehydro- 

 genases (lactic, citric, glucose) were shown to be inhibited by similar 

 concentrations of morphine; levels much higher than any which could 

 be attained in the animal body. The results were interpreted very 



