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 journalArticle

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Abstract

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
Volume50
Issue number5
DOIs
Publication statusPublished - Mar 8 2007

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sigma Receptors
Ligands
Primary Cell Culture
N-Methylaspartate
Cell culture
Adrenergic Agents
Cholinergic Agents
Serotonin
transglutaminase 2

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Prezzavento, O., Campisi, A., Ronsisvalle, S., Li Volti, G., Marrazzo, A., Bramanti, V., ... Ronsisvalle, G. (2007). Novel sigma receptor ligands: Synthesis and biological profile. Journal of Medicinal Chemistry, 50(5), 951-961. https://doi.org/10.1021/jm0611197

Novel sigma receptor ligands : Synthesis and biological profile. / Prezzavento, Orazio; Campisi, Agata; Ronsisvalle, Simone; Li Volti, Giovanni; Marrazzo, Agostino; Bramanti, Vincenzo; Cannavò, Giuseppe; Vanella, Luca; Cagnotto, Alfredo; Mennini, Tiziana; Ientile, Riccardo; Ronsisvalle, Giuseppe.

In: Journal of Medicinal Chemistry, Vol. 50, No. 5, 08.03.2007, p. 951-961.

Research output: Contribution to journalArticle

Prezzavento, O, Campisi, A, Ronsisvalle, S, Li Volti, G, Marrazzo, A, Bramanti, V, Cannavò, G, Vanella, L, Cagnotto, A, Mennini, T, Ientile, R & Ronsisvalle, G 2007, 'Novel sigma receptor ligands: Synthesis and biological profile', Journal of Medicinal Chemistry, vol. 50, no. 5, pp. 951-961. https://doi.org/10.1021/jm0611197
Prezzavento O, Campisi A, Ronsisvalle S, Li Volti G, Marrazzo A, Bramanti V et al. Novel sigma receptor ligands: Synthesis and biological profile. Journal of Medicinal Chemistry. 2007 Mar 8;50(5):951-961. https://doi.org/10.1021/jm0611197
Prezzavento, Orazio ; Campisi, Agata ; Ronsisvalle, Simone ; Li Volti, Giovanni ; Marrazzo, Agostino ; Bramanti, Vincenzo ; Cannavò, Giuseppe ; Vanella, Luca ; Cagnotto, Alfredo ; Mennini, Tiziana ; Ientile, Riccardo ; Ronsisvalle, Giuseppe. / Novel sigma receptor ligands : Synthesis and biological profile. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 5. pp. 951-961.
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