THE THEORY OF AN.ESTHESIA. 325 



homologous series; and it is highly characteristic of such series 

 that the ratio of oil-solubility to water-solubility (oil-water 

 partition-coefficient) increases regularly with increase in molecu- 

 lar weight. At the same time the narcotizing power increases; 

 i. e., in any single series (e. g., alcohols) the higher the molecular 

 weight the lower the concentration required for narcosis. It was 

 this general parallelism that led Overton and Meyer to the view 

 that anaesthetic pow r er, in the case of any substance, is a direct 

 function of its solubility in the fat-like or lipoid constituents of 

 the cell. That a connection exists between the fat-solvent and 

 the anaesthetic properties of a compound had previously been 

 suggested by Bibra and Harless in 1847, and the same view was 

 later expressed by Hermann, C. Bernard, Richet, Ehrlich and 

 others. 1 The first systematic studies of this relationship were 

 however those of Overton and Meyer, the results of whose experi- 

 ments, carried on independently, were published about the same 

 time (1899). 



In a study of the permeability of animal and plant cells to 

 various types of compounds, Overton 2 had reached the conclusion 

 that solubility in lipoids was the chief factor determining the 

 ready entrance of a compound into cells; compounds with well- 

 marked power of penetration belonged chiefly to the narcotic 

 group; and in a later extensive investigation on narcosis in 

 tadpoles 3 a far-reaching parallelism w r as found between the oil- 

 water partition-coefficients of a wide range of organic compounds 

 and their narcotizing action. The nature of Overton's results 

 may be best seen from the following series, which gives the 

 concentrations required to narcotize tadpoles in the case of }he 

 ethyl esters of the first five fatty acids. (See Table I.) 



The narcotic action is seen to increase steadily with decrease 

 in the water-solubility, i. e., increase in the ratio of partition 

 between oil and water. Each member of the series is from two 

 to three times as effective as its immediate predecessor. This 

 rule appears to hold very generally for members of homologous 



1 For an account of these earlier views cf. Overton, "Studien liber die Narkose," 

 June, 1901. 



2 Overton, "On the General Osmotic Properties of Cells," etc., Vierleljahrsschr. 

 d. naturf. Gesellsch. in Zurich, 1899, Vol. 44, p. 88. 



3 "Studien iiber die Narkose," 1901. 



