Serotonin receptor binding affinities of tryptamine analogs

Abstract

Using a rat fundus model, the serotonin (5-HT) receptor binding affinities of 27 tryptamine analogs were determined. Factors which might affect affinity were examined, e.g., lipid solubility, as reflected by partition coefficient and pKa. Structure-activity relationships were developed and were discussed in terms of substituents on the terminal amine, the side chain, and the indole 1 position, the 5 position and at other positions on the indolic nucleus. If lipid solubility and metabolism can be accounted for, there appears to be a parallelism between 5-HT receptor binding affinities and the hallucinogenic (psychotomimetic) potencies of several of these compounds. As first suggested by Woolley, there may be a relationship between the hallucinogenic (psychotomimetic) activity displayed by various N,N-dialkyltryptamine derivatives and their ability to interact with serotonin (5-hydroxytryptamine, 5-HT) receptors in the brain.