Biophysical Factors in Drug Action 15 



/j-aminobenzoic acid is due to the similarity in structure between 

 the drugs and the metabolite, and that owing to this similarity 

 there is a displacement of metabolite from the bacterial enzyme 

 receptors by the competitive action of the drug. This reduction 

 in available substrate results in an inhibition of bacterial growth. 



Tlie "Lipoid Theory" of Narcotic Action 



It is less easy to apply the structural relationships of the re- 

 ceptor theory to the mode of action of depressants or narcotics, 

 where activity appears to depend mainly on the physical proper- 

 ties of the drug molecules rather than on special molecular con- 

 figurations. Here the drugs have a characteristic reversible ac- 

 tion. The numerous relationships between the intensity of a 

 depressant action and the changes in the physical properties of 

 narcotics in homologous series of drugs suggest that there is a 

 physical equilibrium between the drug and some component of 

 the living cell which is narcotic sensitive. If we assume that 

 narcotic action depends on the uptake of the drug by the cell 

 lipids, we can collect a great deal of experimental evidence which 

 supports the coincidence between narcotic action and simple drug 

 chstribution in model systems containing a mixture of oil and 

 water. This relationship forms the basis of the well-known 

 "lipoid theory" of narcosis which was advanced towards the close 

 of the last century by Overton 2^' ^^' -^' ^^ and Meyer.-^ A later 

 generalization by Traube ^^' ^^' ^^ seeks to correlate narcotic ac- 

 tion with the adsorption of drugs at cell surfaces or interfaces. 

 This ''adsorption theory" depends on the parallelism between 

 narcotic activity and the surface activity of drugs, and it is sup- 

 posed that the cell lipids are not ne"cessarily the dominant bio- 

 logical substrates or receptors involved in drug uptake. 



The literature abounds with numerous discussions and criti- 

 cisms of the Overton-Meyer and Traube concepts. These prin- 

 ciples have the outstanding merit of simplicity, and their attrac- 

 tion rests in the abundant evidence that has since accumulated 

 and which lends added support to either theory. An adequate 

 survey of the extensions and modifications of these early gen- 



