The structural requirements for high-affinity binding at the serotonin transporter (SERT) have been investigated through the preparation of some 3-[(aryl)(4-fluorobenzyloxy)methyl]piperidine derivatives. The affinity of synthesised piperidinic compounds (1-4) at the SERT was evaluated by displacement of [H-3]-paroxetine binding. Derived inhibition constant (K-i) values were in the same order of magnitude as that of fluoxetine, ranging between 2 and 400 nM. To better define the profiles of these compounds as potential antidepressants, binding affinity for 5-HT1A receptors and alpha 2-adrenoceptors was also investigated by competition experiments using [H-3]8-hydroxy-2-(dipropylamino)tetralin ([H-3]8-OH-DPAT) and [H-3]rauwolscine as radiolabelled ligands, respectively. Inhibition data indicate that compounds 1-4 possess a very weak affinity for these receptors. The high affinity of compound 1 for SERT indicates that it is worth investigating further.

3-[(aryl)(4-fluorobenzyloxy)methyl]piperidine derivatives: high-affinity ligands for the serotonin transporter

NENCETTI, SUSANNA;DEMONTIS, GIAN CARLO ALFREDO GIUSEPPE;MAZZONI, MARIA ROSA;BETTI, LAURA;ROSSELLO, ARMANDO;LAPUCCI, ANNALINA
2007-01-01

Abstract

The structural requirements for high-affinity binding at the serotonin transporter (SERT) have been investigated through the preparation of some 3-[(aryl)(4-fluorobenzyloxy)methyl]piperidine derivatives. The affinity of synthesised piperidinic compounds (1-4) at the SERT was evaluated by displacement of [H-3]-paroxetine binding. Derived inhibition constant (K-i) values were in the same order of magnitude as that of fluoxetine, ranging between 2 and 400 nM. To better define the profiles of these compounds as potential antidepressants, binding affinity for 5-HT1A receptors and alpha 2-adrenoceptors was also investigated by competition experiments using [H-3]8-hydroxy-2-(dipropylamino)tetralin ([H-3]8-OH-DPAT) and [H-3]rauwolscine as radiolabelled ligands, respectively. Inhibition data indicate that compounds 1-4 possess a very weak affinity for these receptors. The high affinity of compound 1 for SERT indicates that it is worth investigating further.
2007
Nencetti, Susanna; Demontis, GIAN CARLO ALFREDO GIUSEPPE; Mazzoni, MARIA ROSA; Betti, Laura; Banti, I; Rossello, Armando; Lapucci, Annalina
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/180713
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