Novel sigma receptor ligands: Synthesis and biological profile

Orazio Prezzavento, Agata Campisi, Simone Ronsisvalle, Giovanni Li Volti, Agostino Marrazzo, Vincenzo Bramanti, Giuseppe Cannavò, Luca Vanella, Alfredo Cagnotto, Tiziana Mennini, Riccardo Ientile, Giuseppe Ronsisvalle

Research output: Contribution to journalArticlepeer-review


The aim of the present study was to investigate the biological profile of new substituted 1-phenyl-2-cyclopropylmethylamines. High affinity for both σ subtypes was achieved when 4-phenylpiperidin-4-ol (4a-e) and 4-benzylpiperidine moieties were present (5a-e). (1R,2S/1S,2R)-2-[4-Hydroxy-4- phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopropanecarboxylate (4b) showed high affinity for the σ1 sites (Ki = 1.5 nM) and the most favorable σ12 selectivity (Ki2)Ki1) = 33.9). Binding affinity studies showed that 4b binding on N-methyl-D-aspartate (NMDA), dopaminergic (D1, D2, D3), muscarinic, histaminergic H1, adrenergic (α1, á2), serotoninergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT6), DA (DAT), and 5-HT (SERT) transporters was not significant. Interestingly, σ ligands differently induced the expression of tissue transglutaminase (TG-2) in primary astroglial cell cultures. We suggest that 4b may act as a σ1/ σ2 agonist and that the σ ligands may modulate TG-2 differently.

Original languageEnglish
Pages (from-to)951-961
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number5
Publication statusPublished - Mar 8 2007

ASJC Scopus subject areas

  • Organic Chemistry


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