Studies of the relationship between molecular structure and hallucinogenic activity.
Pharmacology, Biochemistry, and Behavior February 1986 DOI: 10.1016/0091-3057(86)90362-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Rats and humans |
| Key findings | The authors propose that a hydrophobic site binds the 4-substituent of phenethylamine hallucinogens with a specific geometry, and report that N(6)-ethyl, allyl, and propyl nor-LSD derivatives matched or exceeded LSD's potency in rat drug discrimination and in humans, whereas N(6)-alkyl groups longer than n-propyl greatly reduced activity. |
Abstract
The nature of the stereochemistry and aromatic ring substituents and their importance to biological activity for phenethylamine-type hallucinogens is presented. The possibility of a hydrophobic site to bind to the 4-substituent and its likely geometry is described. A brief discussion of the structure-activity relationships for tryptamines such as psilocin and DMT is also given, with comments about the stereochemistry of alpha-methyltryptamines. Evaluation of a series of N(6)-alkyl-nor-LSD derivatives indicated that selected members such as N(6)-ethyl, allyl and propyl were as potent as, if not more potent than LSD, both in a two-lever drug discrimination assay in rats, and in man. N(6)-alkyl groups longer than n-propyl, such as n-butyl or 2-phenethyl, gave compounds that were greatly reduced in activity.
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- Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use. Biochemical Pharmacology June 1, 2019
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- High-affinity 3H-serotonin binding to caudate: inhibition by hallucinogens and serotoninergic drugs. Psychopharmacology September 15, 1978
- Correlation of psychotomimetic activity of phenethylamines and amphetamines with 1-octanol-water partition coefficients Journal of Medicinal Chemistry February 1, 1975
- Comparison of solution conformational preferences for the hallucinogens bufotenin and psilocin using 360-MHz proton NMR spectroscopy. Journal of Medicinal Chemistry February 1, 1981
- Stereospecific Actions of DOET (2,5-Dimethoxy-4-Ethylamphetamine) in Man Archives of General Psychiatry July 1, 1974
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