I90 PROTOPLASMIC ACTION AND NERVOUS ACTION 



its oil-water partition-coefficient, a relation first studied 

 systematically by these investigators.' 



In his investigations on permeability, Overton had 

 reached the conclusion that solubility in lipoids was the 

 chief factor determining the entrance of compounds 

 into cells; such readily penetrating compounds belong 

 for the most part to the narcotizing group; and a 

 detailed study of the phenomena of narcosis in tadpoles 

 demonstrated a close parallelism between the relative 

 solubilities of a large number of organic compounds in 

 oil and water and their narcotizing action.^ The ratio 

 according to which any compound is distributed between 

 these solvents (when the solvents are in contact and 

 equilibrium is reached) is a measure of its relative solu- 

 bility in the two; this ratio is known as the ^'partition- 

 coefficient." In the early members of any homologous 

 series of compounds the ratio of oil-solubility to water- 

 solubility increases progressively as the molecular 

 weight increases, and the same is true of the narcotizing 

 properties of the compounds. For example, with the 

 ethyl esters of the first five fatty acids, Overton found 

 the concentrations required for the complete narcosis 

 of tadpoles to be as indicated in the table (p. 191). 



The narcotic effectiveness of the ester increases 

 regularly as its water-solubility decreases; and in 

 general each member of the series is from two to three 

 times as effective as its immediate predecessor. Rela- 

 tions of a similar kind were found with other series, 



^ Overton, Vierteljahrschriften d. Naiurf. Gesellschajt, Ziirich, 

 XLIV (1899), 88; Studien iiber die Narkose (1901); H. H. Meyer, 

 Arch. f. exper. Path. u. Pharmakol., XLII (1899), 109. 



' Studien iiber die Narkose. 



