A novel quantum theoretic QSAR for hallucinogenic tryptamines:: a major factor is the orientation of π orbital nodes

For a series of hallucinogenic tryptamines, activity has been shown to depend mainly on the orientation of one of the nodes in the highest occupied pi-like orbital, and to a lesser degree on the lipophilicity of the amine nitrogen substituents. This agrees with previous work on phenylalkylamine hallucinogens. At least 74% of the variance in log activity can be explained in terms of the angular variable alone. This conflicts with the common view that interaction of a ligand with a receptor is explicable in classical rather than quantum theoretic terms. The activity of the beta-carboline hallucinogen harmaline is also accounted for by this QSAR without further assumptions, however, those of the very potent ergoline hallucinogens, that include an extra double bond conjugated to the aromatic ring system, are not. (C) 2004 Elsevier B.V. All rights reserved.