Molecular Pharmacology, Vol 12, 605-611, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Self-association and Binding Sites of Some Psychotomimetic Tryptamine Derivatives and Related Compounds: Nuclear Magnetic Resonance Investigations

¹ Institut für Biophysik der Universität, D-63 Giessen, and Institut für Biochemie, GSF, D-8042 Neuherberg, Federal Republic of Germany

The nature of the binding sites in the self-association of some psychotomimetic drugs has been investigated by NMR techniques. In the case of d-lysergic acid diethylamide the interaction of the aromatic ring systems was found to be the basis of self-association (H = -8.7 ± 0.7 kcal mole^-1). In self-associates of the tryptamine derivatives and mescaline (H = -3 to -4 kcal mole^-1) the ring overlap of associated molecules may be replaced by an alignment of the amino group located at the end of the side chain with the ring system of a neighboring molecule. The influence of substitutions on the ring systems and special solvent-solute interactions is discussed. Whereas the amino group at the end of the side chain seems to be the preferred site of solvent-solute interactions, the locus of a hydroxyl substitution on the ring system seems to modify the stereochemistry of the self-associates.