Steric and Electronic Relationships among Some Hallucinogenic Compounds
Sungzong Kang, Jack Peter Green
Proceedings of the National Academy of Sciences September 1, 1970 DOI: 10.1073/pnas.67.1.62 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | LSD Mescaline |
| Keywords | Hallucinogen Steric effects Stereochemistry Pyrrole Heteroatom Ring chemistry Receptor Organic chemistry Pharmacology Biochemistry |
| Citations | 64 |
| Key points | Proposes that LSD, indolealkylamines, and methoxylated amphetamines share stereochemical and electronic features that allow them to interact with a common receptor via π-molecular and donor-acceptor complexes. |
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.