Molecular determinants for binding of methylenedioxytryptamines at 5-HT/LSD receptors
International Journal of Quantum Chemistry March 5, 1981 Patricia H. Reggio, Harel Weinstein, Roman Osman et al. 17 citations
A mechanistic hypothesis explains how drugs are recognized by a serotonin (5-HT) receptor in the brain that also binds LSD. The hypothesis links a drug's affinity for this receptor to an intramolecular rearrangement that aligns the electrostatic orientation vector of its indole portion with that of serotonin itself. To test this, a new series of tryptamine derivatives with methylenedioxy substituents at the 5,6 or 4,5 positions was studied. Their reactivity characteristics and theoretical predictions for activity at the 5-HT/LSD receptor are presented, based on electrostatic potential comparisons and simulations of molecular interactions with an imidazolium cation probe. Preliminary experimental binding data for these derivatives confirm that affinity can be predicted by the hypothesis.