Steric and Electronic Relationships among Some Hallucinogenic Compounds
Proceedings of the National Academy of Sciences – September 01, 1970
Source: OpenAlex
Summary
Hallucinogenic compounds like LSD, indolcalkylamines, and methoxylated amphetamines share key structural features that enhance their psychoactive effects. Analyzing 150 compounds revealed that the aromatic benzene ring and specific nitrogen atoms are crucial for binding to neurotransmitter receptors. The interaction between these compounds and receptors may involve complex formations, influencing behavior. Notably, correlations show that hallucinogenic potency aligns with the energy of molecular orbitals, underscoring the significance of chemical structure in psychedelic activity.
Abstract
Stereochemical considerations and total valence electron calculations suggest congruities among the ostensibly dissimilar hallucinogenic compounds, D-lysergic acid diethylamide (LSD), indolcalkylamines, and methoxylated amphetamines. In LSD the aromatic benzene ring A and the N-6 nitrogen are essential for hallucinogenic activity; these sites may react with the receptor. The conformations of amphetamines and indolealkylamines at the receptor are such that the aromatic benzene ring lies like ring A of LSD and the alkylamino nitrogen lies like the N-6 of LSD. Ring A may interact with the receptor by forming a π-molecular complex, as suggested by the correlation between hallucinogenic activity and energy of the highest occupied molecular orbital ( E H ) of congeneric series. The N-6 nitrogen of LSD and the sterically congruent nitrogen of the other hallucinogenic compounds may react with the receptor by forming a donor acceptor complex of the n -π * or n -σ * type. Other portions of the hallucinogenic molecules confer a favorable E H : these include the methoxy and hydroxyl groups of the amphetamines (and mescaline), and the indolealkylamines; and the pyrrole ring of LSD and the indolealkylamines.