Detailed In vitro pharmacological characterization of the clinically viable NOP receptor agonist Sunobinop

NOP receptor is a G protein-coupled receptor belonging to the opioid family of receptors. NOP and its endogenous agonist the neuropeptide nociceptin/orphanin FQ (N/OFQ) play an important role in modulating various biological functions, and recently their role in modulating sleep/insomnia has been highlighted. Sunobinop was described as a very effective hypnotic, capable of fostering sleep in rodents and patients. In the thesis, several in vitro assays have been employed to fully characterize Sunobinop pharmacological effects. In particular, we detected NOP-Gβ1 protein interaction, cAMP level inhibition, and NOP-mediated bioimpedance alteration in cells expressing the human recombinant receptor. The effects of Sunobinop were systematically compared to those of N/OFQ and a panel of standard NOP agonists including UFP-113, MCOPPB, and AT-403.