A. D. WELCH AND E. BUEDING 



cautiously by the investigators and serve as a basis for the further 

 studies which are needed. 



More recently, Mayer and McCawley (21) have shown that 

 the N-allyl homologue of morphine is even more depressant of oxygen 

 consumption by slices of rat cerebrum than is morphine. Other 

 studies (13,18,35) have shown, however, that this derivative is antago- 

 nistic to many of the effects produced by morphine, particularly that 

 of respiratory depression. It would appear that depression of oxida- 

 tive reactions of brain tissue, in vitro, cannot serve to explain the 

 differences between the effects of morphine and the allyl homologue 

 and certainly cannot account for the narcotic and analgesic actions of 

 the parent alkaloid. 



A striking observation made during the biochemical studies of 

 Shideman and Seevers (33) is worthy of note. They found that the 

 chronic administration of morphine to rats leads to a sustained accel- 

 eration in the oxidative metabolism of skeletal muscle, an effect which is 

 maintained when morphine has been withdrawn, and which is noted 

 when a major portion of the morphine would have been eliminated 

 from the body. The addition of morphine to muscle tissue, in vitro, 

 produces an increase in oxygen uptake, an effect observed whether the 

 tissue used is obtained from normal rats or from chronically mor- 

 phinized animals with an initial rate of oxygen consumption nearly 

 twice that of the muscle tissue of normal rats. Shideman and Seevers 

 do not believe that these observations are to be accounted for by the 

 oxidation of the drug. As was pointed out, the data available do not 

 clearly associate the effects produced in vitro with those which occur 

 uniformly in chronically morphinized muscle during withdrawal. 

 The fact that a concentration of azide which is without effect on the 

 respiration of normal muscle reduces to an approximately normal level 

 the oxygen utilization of chronically morphinized muscle should also 

 be mentioned. These interesting observations suggest the need for 

 additional studies of the mechanism of action of this very important 

 drug. 



On the basis of studies in their own laboratory (9) and else- 

 where (3), Gaddum and Kwiatkowski advanced the hypothesis that 

 the action of ephedrine, a naturally occurring sympathomimetic com- 

 \ pound chemically related to epinephrine, can best be accounted for 

 by its inhibition of amine oxidase. This enzyme is one of several which 



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