Evaluation of the analgesic effect of 4-anilidopiperidine scaffold containing ureas and carbamates. (1st November 2016)

• Record Type: Journal Article
• Authors: Monti, Ludovica; Stefanucci, Azzurra; Pieretti, Stefano; Marzoli, Francesca; Fidanza, Lorenzo; Mollica, Adriano; Mirzaie, Sako; Carradori, Simone; De Petrocellis, Luciano; Schiano Moriello, Aniello; Benyhe, Sándor; Zádor, Ferenc; Szűcs, Edina; Ötvös, Ferenc; Erdei, Anna I.; Samavati, Reza; Dvorácskó, Szabolcs; Tömböly, Csaba; Novellino, Ettore
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 6(2016:Dec.)
• Page Start: 1638
• Page End: 1647
• Publication Date: 2016-11-01
• Subjects: Fentanyl -- FAAH enzyme -- MAGL enzyme -- opioids -- pain; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2016.1160902
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs. In this paper we report the synthesis, characterization and biological evaluation of twelve new 4-anilidopiperidine (fentanyl analogues). In vivo hot-Plate test, shows a moderate antinociceptive activity for compoundsOMDM585 andOMDM586, despite the weak binding affinity on both μ and δ-opioid receptors. A strong inverse agonist activity in the GTP-binding assay was revealed suggesting the involvement of alternative systems in the brain. Fatty acid amide hydrolase inhibition was evaluated, together with binding assays of cannabinoid receptors. We can conclude that compoundsOMDM585 and586 are capable to elicit antinociception due to their multitarget activity on different systems involved in pain modulation.