THE THEORY OF ANESTHESIA. 327 



of lipoid-soluble substances into cells. Now it is an evident 

 corollary of Overton's hypothesis that if the anaesthetic acts 

 by changing the physical state of the lipoid cell-constituents it 

 must affect the properties of a lipoid-rich cell-structure like the 

 plasma-membrane. Overton, however, does not refer narcotic 

 action specifically to a modification of the plasma-membrane 

 alone, but to a general modification in the physical state of all 

 cell-lipoids, wherever situated. Recently, however, much evi- 

 dence has accumulated indicating that the essential influence is 

 that exerted on the plasma-membrane, and that it is the modifica- 

 tion in the properties of this structure which determines the 

 characteristic anaesthetic effect. This evidence and its implica- 

 tions will be considered later. 



The hypothesis of Overton and Meyer has received wide 

 acceptance. It is not clear, however, why simple solution of 

 chemically indifferent substances in the lipoids of the tissue 

 should so modify its irritability; and Overton and Meyer do not 

 attempt to explain this connection. The parallelism between 

 lipoid-solubility and narcotic action is not an exact one, and 

 many exceptions to the rule are known. The powerful narcotic 

 action of chloral hydrate, which is several times more soluble in 

 water than in oil, is not thus explained; and lipoid-insoluble 

 neutral salts of magnesium and other metals may exert typical 

 narcotic action. Evidently other factors than solubility may 

 enter. Yet the evidence adduced by Overton and Meyer, as 

 well as by more recent investigators, leaves no doubt that in the 

 case of organic anaesthetics high lipoid-solubility is typically 

 associated with marked narcotic action. The reversibility of 

 anaesthesia corresponds to the reversibility of the process of 

 solution. The chemical indifference of many anaesthetics is thus 

 not surprising, since the substance acts not by chemical combina- 

 tion but by simple solution in the cell-lipoids. 



According to Overton and Meyer's hypothesis it is this solution 

 of the narcotic in the lipoid which determines anaesthetic action. 

 This view has recently been attacked from various sides. Ac- 

 cording to Traube, 1 the anaesthetic acts not by dissolving in the 



1 I. Traube, "Theorieder Narkose," Pfluger's Archiv, 1913, Vol. 153, p. 276, and 

 Vol. 160, 1915, p. 501; also "Theorie des Haftdrucks und Lipoidtheorie," Biochem- 

 Zeitschr., 1913, Vol. 54, p. 305, and other papers cited there. 



