Background: Serotonin is an important biogenic amine and is implicated in wideranging
physiological and physiopathological processes. Pharmacological manipulation of the serotoninergic
system is believed to have a great therapeutic potential.
Objectives: In order to identify selective ligands for 5-HT1A, 5-HT2A and 5-HT2C receptors two series
of 4-substituted piperazine derivatives, bearing indolic or methyl indolic nuclei, were synthesized.
Methods: All the compounds, synthesized by standard solution methods, were evaluated for 5-
HT1A, 5-HT2A and 5-HT2C receptors. The highest affine and selective compounds have been
evaluated also on dopaminergic (D1 and D2) and adrenergic (α1A and α2A) receptors.
Results: Several of the newly synthesized molecules showed affinity in the nanomolar range for 5-
HT1A, 5-HT2A and 5-HT2C receptors and moderate to no affinity for other relevant receptors (D1,
D2, α1A and α2A).
Conclusion: Compounds 7f and 10a showed a nanomolar affinity towards 5-HT1A with an in vitro
pharmacologic profile compatible with antipsychotic drugs.