AUGUST 19, 1921 AI.SBERG : PHYSIOLOGICAL CHEMISTRY 329 



pendent apparently upon a common physical property exhibited by 

 substances of the most diverse chemical structure. ^^ 



That this relation is not accidental is proven by the fact that the 

 narcotic power of these substances is broadly proportional to their 

 relative solubility in oil as compared with their solubility in water; 

 that is, proportional to their distribution coefficient between these 

 two solvents. The more this ratio is in favor of oil the more narcotic 

 the substance. This was proved for a large number of substances, 

 both by H. Meyer- and by Overton'-^ who experimented with tad- 

 poles. These animals were placed in water containing varying con- 

 centrations of the substance to be tested and the effect noted. In 

 this way the lowest concentration capable of narcotizing the tadpoles 

 was determined. Comparison of the minimum narcotic concentration 

 thus determined for a large number of substances demonstrated that 

 these concentrations show a direct parallelism with the distribution 

 coefficients of the respective narcotics between oil and water. 



This parallelism of the effective narcotic strength of a substance with 

 its oil-water distribution coefficient is demonstrated strikingly if 

 experiments be made, as was done by Meyer-^ with the same sub- 

 stances at different temperatures. The narcotic power of each sub- 

 stance changes with the temperature in proportion to the shift made 

 by the temperature in the oil-water distribution coefficient. This is 

 especially striking in the case of chloral as will appear from an ex- 

 amination of table 1 which has been adapted from Meyer's publication 

 on this subject. 



It is obvious that experiments analogous to Overton's tadpole experi- 

 ments can be performed upon animals breathing through lungs instead 

 of gills only with volatile narcotics like ether or chloroform. The 

 non-volatile narcotics cannot be tested in any direct way because 

 when given by the mouth the rate of absorption from the alimentary- 

 tract may vary in different individuals and in the same individual at 

 different times. Moreover the rate varies with the solubility of the 

 narcotic in the contents of the intestinal tract. Thus phenanthrene is 

 not sufficiently soluble in water to be absorbed and exert any action 

 though it has actually narcotic power. Long ago Bert showed that 



2' L. Hermann, op. cit. 



" H. Meyer, op. cit. 



" E. Overton, op. cit. 



** H. Meyer, Zur Theorie der Alkohol Narkose. Ill Mittheilung. Der Etnfluss wech- 

 selnder Tetnperatur auf Wirkungstdrke und Theilungs-Coefficient der Narcotica. Arch, 

 exp. Path. u. PharmakoL 46: 338. 1901. 



