Stereospecific Actions of DOET (2,5-Dimethoxy-4-Ethylamphetamine) in Man
Archives of General Psychiatry – July 01, 1974
Source: OpenAlex
Summary
The (-) "R" isomer of DOET, a psychedelic methoxyamphetamine, demonstrates approximately four times the potency of its (+) "S" counterpart in inducing psychotropic effects among normal human subjects. This finding highlights how specific molecular conformations can significantly influence the psychedelic experience, paralleling effects seen in other hallucinogens like mescaline and LSD. With a sample size of 30 participants, the study sheds light on the importance of stereochemistry in drug activity, paving the way for deeper understanding in natural compound pharmacology and psychedelics.
Abstract
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 andd-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.