July 1974

Stereospecific Actions of DOET (2,5-Dimethoxy-4-Ethylamphetamine) in Man

Author Affiliations

Baltimore; Iowa City
From the departments of pharmacology and experimental therapeutics and psychiatry and the behavorial sciences, the Johns Hopkins University School of Medicine, Baltimore (Dr. Snyder); the Maryland Psychiatric Research Center, Baltimore (Dr. Unger and R. Blatchley); and the College of Pharmacy, University of Iowa, Iowa City (Dr. Barfknecht).

Arch Gen Psychiatry. 1974;31(1):103-106. doi:10.1001/archpsyc.1974.01760130079013

Several different molecular conformations of psychedelic drugs have been proposed to explain the very similar effects of drugs with markedly divergent chemical structures, such as mescaline and d-lysergic acid diethylamide (LSD). In some of these models, the α-carbon of methoxyamphetamine psychedelics approximates the asymmetric carbon No. 5 of LSD predicting that the (-) "R" isomer of the methoxyamphetamines should possess greater psychedelic activity than the ( + ) "S" isomer.

The present study reports a comparison of the psychotropic effects of isomers of DOET (2,5-dimethoxy-4-ethylamphetamine) a "psychedelic" methoxyamphetamine, in normal human subjects. The (-) "R" isomer is about four times as potent as the ( + ) "S" isomer, thus specifying the psychoactive conformation of the drug. This clinical study represents a novel approach to determining the molecular conformation of a drug at its receptor site.