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Studies of the relationship between molecular structure and hallucinogenic activity

1986; Elsevier BV; Volume: 24; Issue: 2 Linguagem: Inglês

10.1016/0091-3057(86)90362-x

1873-5177

David E. Nichols,

Neurotransmitter Receptor Influence on Behavior

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 abouth th 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.