TY - JOUR T1 - Detailed in vitro pharmacological characterization of the clinically viable NOP receptor antagonist BTRX-246040 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.119.262865 SP - jpet.119.262865 AU - Federica Ferrari AU - Sabrina Rizzo AU - Chiara Ruzza AU - Girolamo Calo Y1 - 2020/01/01 UR - http://jpet.aspetjournals.org/content/early/2020/01/14/jpet.119.262865.abstract N2 - The peptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the N/OFQ receptor (NOP) which is widely expressed in the central and peripheral nervous system. Selective NOP antagonists are worthy of testing as innovative drugs to treat depression, Parkinson disease, and drug abuse. The aim of this study was to perform a detailed in vitro characterization of the novel NOP antagonist BTRX-246040. BTRX-246040 has been tested in vitro in the following assays: calcium mobilization in cells expressing NOP and classical opioid receptors and chimeric G proteins, BRET assay measuring NOP interaction with G proteins and β-arrestins, the label free dynamic mass redistribution assay, and the electrically stimulated mouse vas deferens. BTRX-246040 was systematically compared to the standard NOP antagonist SB-612111. In all assays BTRX-246040 behaves as a pure and selective antagonist at human recombinant and murine native NOP receptors displaying 3 - 10 fold higher potency than the standard antagonist SB-612111. BTRX-246040 is as an essential pharmacological tool to further investigate the therapeutic potential of NOP antagonists in preclinical and clinical studies.SIGNIFICANCE STATEMENT NOP antagonists may be innovative antidepressant drugs. In this research BTRX-246040 has been deeply characterized in vitro in a panel of assays. BTRX-246040 resulted a pure, potent and selective NOP antagonist. ER -