Molecular Pharmacology, Vol 18, 455-460, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Approximate Molecular Potentials of Mescaline Analogues in a Study of Similarities to 5-Hydroxytryptamine

¹ Department of Pharmaceutical Chemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298

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.