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[(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor.
J Pharmacol Exp Ther 2005; 312(3):1114-23JP

Abstract

A novel ligand for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102), has been generated by combining in the N/OFQ-NH(2) sequence two chemical modifications, [Arg(14),Lys(15)] and [(pF)Phe(4)], that have been previously demonstrated to increase potency. In vitro, UFP-102 bound with high affinity to the human NOP receptor, showed at least 200-fold selectivity over classical opioid receptors, and mimicked N/OFQ effects in CHO(hNOP) cells, isolated tissues from various species, and mouse cortical synaptosomes releasing 5-hydroxytryptamine. UFP-102 showed similar maximal effects but higher potency (2- to 48-fold) relative to N/OFQ. The effects of UFP-102 were sensitive to NOP-selective antagonists J-113397 [(+/-)-trans-1-[1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] (pA(2) = 7.75-8.12) and UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2))(pA(2) = 6.91-7.33) but not to naloxone, and no longer observed in tissues taken from NOP receptor knockout mice (NOP(-/-)). In vivo, UFP-102 (0.01-0.3 nmol i.c.v.) mimicked the pronociceptive action of N/OFQ (0.1-10 nmol i.c.v.) in the mouse tail withdrawal assay, displaying higher potency and longer lasting effects. The action of UFP-102 was not apparent in NOP(-/-) mice. Similar results were obtained measuring locomotor activity in mice. In conscious rats, UFP-102 (0.05 nmol i.c.v.) produced a marked and sustained decrease in heart rate, mean arterial pressure, and urinary sodium excretion and a profound increase in urine flow rate. These effects were comparable with those evoked by N/OFQ at 5 nmol. Collectively, these findings demonstrate that UFP-102 behaves as a highly potent and selective NOP receptor agonist that produces long-lasting effects in vivo.

Authors+Show Affiliations

Department of Experimental and Clinical Medicine, Section of Pharmacology, via Fossato di Mortara 19, 44100 Ferrara, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15509719

Citation

Carrà, Giacomo, et al. "[(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a Highly Potent and Selective Agonist of the Nociceptin/orphanin FQ Receptor." The Journal of Pharmacology and Experimental Therapeutics, vol. 312, no. 3, 2005, pp. 1114-23.
Carrà G, Rizzi A, Guerrini R, et al. [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor. J Pharmacol Exp Ther. 2005;312(3):1114-23.
Carrà, G., Rizzi, A., Guerrini, R., Barnes, T. A., McDonald, J., Hebbes, C. P., ... Calo', G. (2005). [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor. The Journal of Pharmacology and Experimental Therapeutics, 312(3), pp. 1114-23.
Carrà G, et al. [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a Highly Potent and Selective Agonist of the Nociceptin/orphanin FQ Receptor. J Pharmacol Exp Ther. 2005;312(3):1114-23. PubMed PMID: 15509719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [(pF)Phe4,Arg14,Lys15]N/OFQ-NH2 (UFP-102), a highly potent and selective agonist of the nociceptin/orphanin FQ receptor. AU - Carrà,Giacomo, AU - Rizzi,Anna, AU - Guerrini,Remo, AU - Barnes,Timothy A, AU - McDonald,John, AU - Hebbes,Christopher P, AU - Mela,Flora, AU - Kenigs,Velga A, AU - Marzola,Giuliano, AU - Rizzi,Daniela, AU - Gavioli,Elaine, AU - Zucchini,Silvia, AU - Regoli,Domenico, AU - Morari,Michele, AU - Salvadori,Severo, AU - Rowbotham,David J, AU - Lambert,David G, AU - Kapusta,Daniel R, AU - Calo',Girolamo, Y1 - 2004/10/27/ PY - 2004/10/29/pubmed PY - 2005/4/6/medline PY - 2004/10/29/entrez SP - 1114 EP - 23 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 312 IS - 3 N2 - A novel ligand for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102), has been generated by combining in the N/OFQ-NH(2) sequence two chemical modifications, [Arg(14),Lys(15)] and [(pF)Phe(4)], that have been previously demonstrated to increase potency. In vitro, UFP-102 bound with high affinity to the human NOP receptor, showed at least 200-fold selectivity over classical opioid receptors, and mimicked N/OFQ effects in CHO(hNOP) cells, isolated tissues from various species, and mouse cortical synaptosomes releasing 5-hydroxytryptamine. UFP-102 showed similar maximal effects but higher potency (2- to 48-fold) relative to N/OFQ. The effects of UFP-102 were sensitive to NOP-selective antagonists J-113397 [(+/-)-trans-1-[1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] (pA(2) = 7.75-8.12) and UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2))(pA(2) = 6.91-7.33) but not to naloxone, and no longer observed in tissues taken from NOP receptor knockout mice (NOP(-/-)). In vivo, UFP-102 (0.01-0.3 nmol i.c.v.) mimicked the pronociceptive action of N/OFQ (0.1-10 nmol i.c.v.) in the mouse tail withdrawal assay, displaying higher potency and longer lasting effects. The action of UFP-102 was not apparent in NOP(-/-) mice. Similar results were obtained measuring locomotor activity in mice. In conscious rats, UFP-102 (0.05 nmol i.c.v.) produced a marked and sustained decrease in heart rate, mean arterial pressure, and urinary sodium excretion and a profound increase in urine flow rate. These effects were comparable with those evoked by N/OFQ at 5 nmol. Collectively, these findings demonstrate that UFP-102 behaves as a highly potent and selective NOP receptor agonist that produces long-lasting effects in vivo. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15509719/[_pF_Phe4Arg14Lys15]N/OFQ_NH2__UFP_102__a_highly_potent_and_selective_agonist_of_the_nociceptin/orphanin_FQ_receptor_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15509719 DB - PRIME DP - Unbound Medicine ER -