GLUCOSE AND OXYGEN UTILIZATION IN SYMPATHETIC GANGLIA 111 



tion in vitro. Determinations have been carried out of the rates of oxygen 

 consumption of homogenates, exposed in the Warburg apparatus, to increasing 

 concentrations of methyl, ethyl, n-propyl and n-butyl alcohols. There is no 

 question but that high enough concentrations can severely depress oxygen 

 consumption. It is also apparent that these concentrations are much higher 

 than those necessary to alter excitability, as well as those in the blood of indi- 

 viduals who are unquestionably "under the influence" of alcohol. Again the 

 findings would indicate an initial membrane effect (reflected, presumably, as 

 changes in polarization) not involved with oxidative mechanisms. 



These effects of alcohol on activity and oxidative mechanisms appear to be 

 very similar to those of a large group of sedative and hypnotic drugs (narcotics). 

 Narcotics too, have been shown to stimulate before they depress. Moreover, 

 common physico-chemical mechanisms must be responsible for the induction 

 of narcosis (as well as for recovery from it), inasmuch as so many structurally 

 different compounds are effective (alcohols, barbiturates, urethanes, etc.). 



Many factors possibly associated with narcosis have been suggested as being 

 the foci of these common mechanisms, among them the relative solubilities of 

 various compounds in the lipoid and protein phases of the cell membrane, 

 interference with respiratory enzymes, and blocking of oxidative breakdown 

 and high energy phosphate bond production in the cell. Much work has been 

 concerned primarily with the biochemical reactions in the cell which revolve 

 around the utilization and synthesis of adenosinetriphosphate (ATP). It has 

 been suggested that narcotics interfere with the direct acetylation process. 

 Recent studies show that this is not the case (alcohols included). Some investi- 

 gations appeared to indicate that the answer lay in direct suppression of the 

 oxidative synthesis of ATP or in uncoupling of phosphorylation from oxidation. 

 That synthesis is not interfered with is shown by recent results in our labora- 

 tories; that uncoupling is not the answer is indicated by the fact that dinitro- 

 phenol, gramicidin and aureomycin, which are among the most effective un- 

 coupling agents, are not known to have any significant narcotic or anesthetic 

 properties. 



Many investigators have suggested effects on brain respiration. However, 

 generalized inhibition of respiration is not what one should look for. Narcotics 

 and anesthetics— and alcohols — in sufficient concentration significantly inhibit 

 oxygen consumption of cerebral tissue. However, several points are of impor- 

 tance here. The first is the problem of concentration of the narcotic. Many of 

 these substances in physiological concentration do not inhibit respiration — in 

 fact, low enough concentrations may even stimulate. Concentration is not the 

 basic factor, but it becomes necessary to refer to the thermodynamic activities. 



A second point involved here is that the rate of oxygen consumption is not 

 the primary factor to be dealt with. The oxidative processes may be involved 

 without being reflected by a change in the rate of oxygen consumption. There 



