Abstract

The electrostatic potentials of five substituted phenethylamines have been calculated and compared with that of 5-hydroxytryptamine (5-HT). A common pattern of potentials was found in four of the five phenethylamines and 5-hydroxytryptamine which is associated with a previously postulated 5-HT pharmacophore. These four analogues are qualitatively reported as being hallucinogenic; the fifth analogue is not. A quantitative relationship was found between the hallucinogenic potency in the four phenethylamines and the decline of a negative electrostatic potential in the region between the 3 and 4 phenyl positions, reinforcing previous reports on the quantitative importance of this part of the molecule.