326 RALPH S. LILLIE. 



series, and a large number of similar instances have been collected 

 by Traube and other recent investigators. 1 Numerous other 

 experiments with alcohols, hydrocarbons, aldehydes, ketones, 

 etc., showed a similar increase in narcotic action with increase 

 in the oil-water partition-coefficients. Overton accordingly drew 

 the conclusion that narcotics act by dissolving in certain sub- 

 stances, contained especially in nerve-cells, which resemble fats 

 in their solvent properties; these substances are the lipoids, 

 especially lecithin and cholesterin, which appear to be essential 

 constituents of protoplasm; it is the physical modification of 

 these substances, due to their being charged or impregnated 

 with the lipoid-soluble narcotic, that forms the essential condition 

 of anaesthesia. Meyer's conclusion w r as similar; 2 the narcotiza- 

 bility of cells is thus related to the nature and the proportion of 

 the lipoids present in the protoplasm; the high susceptibility of 

 nerve-cells is probably dependent on their high lipoid-content. 

 The unequal action of different narcotics depends on their unequal 

 partition-coefficients, which determine their distribution in a 

 mixture of water and lipoid substances. The greater the relative 

 lipoid-solubility the larger the proportion of the anaesthetic 

 present in solution in the lipoid cell-constituents when the 

 partition-equilibrium is reached. Hence, if the lipoid-solubility 

 of a substance is very high, extremely dilute solutions may exert 

 anaesthetic action. Overton, for example, found that phenan- 

 threne could narcotize tadpoles in dilutions so low as one part 

 in 1,500,000 of water. 



TABLE I. 



Narcotizing Concentration. 

 Ester. (Mols per Liter). Solubility in Oil and Water. 



Ethyl formate o.ojm-.ogm Oil: water =4:1 



acetate o^m In 15.2 parts \vater; in all parts oil 



propionate oim-.oi2m 50 



butyrate 0043^ " 190 



( isobutyrate) 0057^ " 140 



valerianate 00197/2 ' 500 



Overton's study of permeability had led him to the conclusion 

 that the outer layer or plasma-membrane of cells consists largely 

 of lipoid material; in this way he explained the ready entrance 



1 Cf. Traube, "Theorie der Narkose," Pfluger's Archiv, 1913, Vol. 153, p. 276. 



2 Hans Meyer, Arch. f. exper. Path. u. Pharm., 1899, Vol. 42, p. 109. 



