Further studies on the binding of N1-substituted tryptamines at h5-HT6 receptors

N1-Arylsulfonyl-substituted analogs of N,N-dimethyltryptamine bind at 5-HT6 receptors. Replacement of the aryl moiety with similarly hydrophobic alkyl substituents results in decreased affinity, as does replacement of a benzenesulfonyl moiety with a benzyl group. Current findings indicate that an aryl (or substituted aryl) sulfonyl (rather than alkylsulfonyl or benzyl) moiety is optimal for high-affinity binding, and further suggest that the N1-benzenesulfonyl- and their corresponding N1-benzyltryptamine counterparts bind in a different fashion.

Graphical abstractN1-Alkylsulfonyl- (R = alkyl) and N1-arylsulfonyltryptamines (R = aryl) bind at h5-HT6 serotonin receptors. The latter bind with higher affinity than their N1-benzyltryptamine counterparts, and evidence suggests they might bind in a different manner at h5-HT6 receptors.Figure optionsDownload full-size imageDownload as PowerPoint slide