Studies of the relationship between molecular structure and hallucinogenic activity.
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.
D000818:Animals; D004873:Ergolines / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D006801:Humans; D008635:Mescaline / Q000031:analogs & derivatives / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000494:pharmacology
D004873:Ergolines; D006213:Hallucinogens; D010627:Phenethylamines; D014363:Tryptamines; D008635:Mescaline