| Literature DB >> 17328523 |
Orazio Prezzavento1, Agata Campisi, Simone Ronsisvalle, Giovanni Li Volti, Agostino Marrazzo, Vincenzo Bramanti, Giuseppe Cannavò, Luca Vanella, Alfredo Cagnotto, Tiziana Mennini, Riccardo Ientile, Giuseppe Ronsisvalle.
Abstract
The aim of the present study was to investigate the biological profile of new substituted 1-phenyl-2-cyclopropylmethylamines. High affinity for both sigma 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 sigma1 sites (Ki = 1.5 nM) and the most favorable sigma1/sigma2 selectivity (Ki(sigma2)/Ki(sigma1) = 33.9). Binding affinity studies showed that 4b binding on N-methyl-d-aspartate (NMDA), dopaminergic (D1, D2, D3), muscarinic, histaminergic H1, adrenergic (alpha1, alpha2), serotoninergic (5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT6), DA (DAT), and 5-HT (SERT) transporters was not significant. Interestingly, sigma ligands differently induced the expression of tissue transglutaminase (TG-2) in primary astroglial cell cultures. We suggest that 4b may act as a sigma1/sigma2 agonist and that the sigma ligands may modulate TG-2 differently.Entities:
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Year: 2007 PMID： 17328523 DOI： 10.1021/jm0611197
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446