Binding Characteristics of a Quaternary Amine Analog of Serotonin: 5-HTQ

Abstract

Because tryptamine derivatives typically bind at multiple populations of 5-HT receptors, they are not normally considered as templates for the design of site-selective serotonergic agents. Taking advantage of the proposal that 5-HT3 receptors are ligand-gated ion channel receptors, and that such receptors usually accept positively charged ligands, we synthesized and evaluated the N,N,N-trimethyl quaternary amine analog of serotonin (5-HTQ). 5-HTQ binds at 5-HT3 receptors with ten times the affinity of 5-HT and displays considerable selectivity relative to the other populations of 5-HT receptors. Although 5-HTQ may not readily penetrate the blood-brain barrier, limiting its application for in vivo investigations , it should be useful for in vitro studies.