Pharmacological characterization of the novel nociceptin/orphanin FQ receptor ligand, ZP120: in vitro and in vivo studies in mice

This study reports on the pharmacological characterization of ZP120, a novel ligand of the nociceptin/orphanin FQ (N/OFQ) peptide receptor, NOP. ZP120 is a structure inducing probes modified NOP ligand: Zealand Pharma proprietary SIP technology was used to increase the enzymatic stability and half‐life of peptide. In vitro, ZP120 mimicked the inhibitory effects of N/OFQ in the electrically stimulated mouse vas deferens, showing however higher potency (pEC50 8.88 vs 7.74), lower maximal effects (Emax 69±5% vs 91±2%), and slower onset of action. Like N/OFQ, the effects of ZP120 were not modified by 1 μM naloxone, but they were antagonized by the NOP receptor selective antagonist J‐113397 (pA2 7.80 vs ZP120, 7.81 vs N/OFQ). In vivo, ZP120 mimicked the effects of N/OFQ, producing pronociceptive effects in the tail withdrawal assay and decreased locomotor activity after i.c.v., but not after i.v. administration in mice. ZP120 elicited similar maximal effects as N/OFQ, but it was about 10 fold more potent and its effects lasted longer. In conclusion, the novel NOP receptor ligand ZP120 is a highly potent and selective partial agonist of the NOP receptor with prolonged effects in vivo. British Journal of Pharmacology (2002) 137, 369–374. doi:10.1038/sj.bjp.0704894