Lipophilic Character and Biological Activity of Drugs II: The Parabolic Case

Abstract

In the first part of this review (l), examples were considered in which there was a linear relationship between the response to drug action and the relative lipophilic character of the drug. Relative drug response was defined in terms of log 1/C (pC), where C is the molar concentration of drug producing a standard response; relative lipophilic character was defined by log P, where P is the octanol-water partition coefficient. The present review extends this survey to the more general problem of the nonlinear relationship between pC and log P. The term “drug” is difficult to define. In these discussions it is employed in the widest sense possible. A drug is considered to be any chemical capable of causing a biochemical or biological response. A better term might be pharmacon, which has been employed by Ariens (2). Ever since Meyer (3) and Overton (4) discovered that the narcotic potency of the members of a set of congeners tends to increase as their oil-water partition coefficients increase, there has been interest in defining “lipophilic character” and its role in the activity of drugs. The analyses in this review are all based on the operational definition of lipophilic character by log P from the octanol-water system. There is, of course, great advantage in using a single reference system. The reasons behind the choice of octanol-water were discussed previously (1, 5) . It is possible to compare work in other solvent systems with that obtained in octanol-water oiu Eq. 1 :