D2 Dopaminergic and 5-HT1A Serotonergic Activity of 2-(1-Naphthyl)ethyl- and 2-(2-Naphthyl)ethyl Amines

Abstract

Several tertiary 2-phenylethyl, 2-(1-naphthyl)ethyl and 2-(2-naphthyl) ethyl amines were synthesized and their binding affinities for dopamine D 1, D2 and serotonin 5-HT1A receptors evaluated in radioligand binding assays. All compounds were inactive in D1 dopamine radioligand binding assay. The 2-(1-naphthyl)ethyl analogues expressed a low but significant binding affinity for the D2 and moderate one for the 5-HT1A receptor subtypes. Most of the remaining compounds expressed binding affinity at the 5-HT1A receptor subtype but were inactive in D2 receptor binding assay. Based on these results and considering the chemical characteristics of the compounds synthesized and evaluated for dopaminergic and serotonergic activity throughout the present study it can be concluded that hydrophobic type of interaction (stacking or edge-to-face) plays a significant role in the formation of receptor-ligand complexes of 2-(1-naphthyl)ethyl amines. This structural motive can be applied to design and synthesize new, more potent dopaminergic/serotonergic ligands by slight chemical modifications.