PARABOLIC DEPENDENCE OF DRUG ACTION UPON LIPOPHILIC CHARACTER AS REVEALED BY A STUDY OF HYPNOTICS

Evidence is presented that the hypnotic activity of groups of barbiturates depend almost entirely on their relative lipophilic character as defined by their octanol-water partition coefficients. Ideal lipophilic character is defined for each set by the constant log P0. This constant for the barbiturates is about 2. It is shown that many other sets of hypnotics structurally unrelated to the barbiturates also have log P0 values near 2. It, is also shown that the rate of metabolism of barbiturates is linearly related to their partition coefficients. Certain guidelines are suggested for the design of new CNS depressants. © 1968, American Chemical Society. All rights reserved.