Pharmacological characterization of the novel nociceptin/orphanin FQ receptor ligand, ZP120: in vitro and in vivo studies in mice.
1 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. 2 In vitro, ZP120 mimicked the inhibitory effects of N/OFQ in the electrically stimulated mouse vas deferens, showing however higher potency (pEC(50) 8.88 vs 7.74), lower maximal effects (E(max) 69+/-5% vs 91+/-2%), and slower onset of action. Like N/OFQ, the effects of ZP120 were not modified by 1 micro M naloxone, but they were antagonized by the NOP receptor selective antagonist J-113397 (pA(2) 7.80 vs ZP120, 7.81 vs N/OFQ). 3 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. 4 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.
Rizzi
Anna
A
Department of Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, University of Ferrara, via Fossato di Mortara, 17, 44100 Ferrara, Italy.
Rizzi
Daniela
D
Marzola
Giuliano
G
Regoli
Domenico
D
Larsen
Bjarne Due
BD
Petersen
Jorgen Soberg
JS
Calo'
Girolamo
G
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009292:Narcotic Antagonists; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000378:metabolism* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D001562:Benzimidazoles; D008024:Ligands; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D010880:Piperidines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C404152:CAM 6369; C402921:J 113397; C473470:ZP120; C000722287:Oprl1 protein, mouse