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New Serotoninergic Ligands Containing Indolic and Methyl Indolic Nuclei: Synthesis and In Vitro Pharmacological Evaluation

[ Vol. 16 , Issue. 4 ]

Author(s):

Elisa Magli, Beatrice Severino*, Angela Corvino, Elisa Perissutti, Francesco Frecentese, Irene Saccone, Flavia Giordano, Marián Castro, José Brea, María I. Loza, Vincenzo Santagada, Giuseppe Caliendo and Ferdinando Fiorino   Pages 517 - 530 ( 14 )

Abstract:


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.

Keywords:

Arylpiperazine derivatives, binding assay, indolic and methyl indolic nuclei, synthesis, serotonin, 5-HT1A, 5-HT2A and 5-HT2C receptor ligands.

Affiliation:

Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, USEF Screening Platform-BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, USEF Screening Platform-BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, USEF Screening Platform-BioFarma Research Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli, Dipartimento di Farmacia, Universita degli Studi di Napoli “Federico II”, Via D. Montesano, 49, 80131, Napoli

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