Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain
Abstract
1. Introduction
2. Structure of NOP Receptor
3. The Distribution and Signaling Pathway of NOP Receptor
4. Ligands of NOP Receptor
4.1. Peptide Ligands Related to N/OFQ Targeting Pain
4.1.1. [Nphe1]N/OFQ(1-13)NH2
4.1.2. [Nphe1, Arg14, Lys15]N/OFQ-NH2 (UFP-101)
4.1.3. [(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-112)
4.1.4. [Phe1Ψ(CH2-NH)Gly2(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-113)
4.1.5. PWT2-N/OFQ
4.2. Non-Peptide NOP Receptor Ligands Targeting Pain
4.2.1. Ro 65-6570
4.2.2. Ro 64-6198
4.2.3. SCH221510
4.3. Bifunctional and Mixed NOP Receptor Compounds
4.3.1. SR 16435
4.3.2. AT-121
4.3.3. Buprenorphine and Its Analog BU08028
4.3.4. BPR1M97
4.3.5. BU10038
4.3.6. JTC-801
4.3.7. Cebranopadol
5. Future Directions and Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name/Structure | Category | In Vitro Human NOP Receptor | In Vivo | Ref | |||
---|---|---|---|---|---|---|---|
Receptor Binding pKi | [35S]GTPγS pKB/pA2 | Ca+2 Mobilization pKB/pA2 | Administration Route/Dose/Species | Effect | |||
[Nphe1]N/OFQ(113)NH2 | Selective NOP receptor antagonist | 8.39 | 7.33 | 6.29 | (30 nmol) i.c.v. mice | Analgesia Promote morphine-induced analgesia. | [61] |
[Nphe1, Arg14, Lys15]N/OFQ-NH2 (UFP-101) | Selective NOP receptor antagonist | 10.24 | 8.85 | 7.66 | (10 nmol) i.c.v. mice | Long lasting analgesia Block N/OFQ effect on locomotor activity | [62] |
(10 nmol) i.t. mice | Block N/OFQ (i.t.1 nmol) analgesic effect | [66] | |||||
[(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-112) | Selective NOP receptor agonist | 10.55 | 10.55 | 9.05 | (1–100 pmol) i.c.v. mice | Hyperalgesia Decrease locomotor activity | [67] |
(1–100 pmol) i.t. mice | Long lasting dose dependent analgesia | [67] | |||||
(0.1 and 10 nmol/kg) Intravenous (i.v.) rats | Decrease heart rate Decrease blood pressure Decrease urinary sodium excretion Increase urine flow | [67] | |||||
(1–10 nmol) i.t. monkey | Dose-dependent analgesia without inducing itch Promotes morphine-induced analgesia without increasing itch response | [68] | |||||
[Phe1Ψ(CH2-NH)Gly2(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-113) | Selective NOP receptor partial agonist | 10.26 | 9.72 | 7.97 | (0.001–1 nmol) i.t. rats | Analgesia | [69] |
PWT2-N/OFQ | Selective NOP receptor agonist | 10.3 | 10.12 | 8.83 | (250 pmol) i.c.v. mice | Decease locomotor activity | [70] |
(2.5–250 pmol) i.t. mice | Dose-dependent analgesia | [71] | |||||
(0.3, 1, and 3 nmol) i.t. monkey | Analgesia No itching No sedation No impairment in motor activity | [71] |
Name/Structure | Category | In Vitro Human NOP Receptor | In Vivo | Ref | |||
---|---|---|---|---|---|---|---|
Receptor Binding pKi | [35S]GTPγS pEC50 | Ca+2 MobilizationpEC 50 | Administration Route/Dose/Species | Effect | |||
Ro 65-6570 | NOP receptor non peptide agonist | 8.6 | (0.1–1 mg/kg) (0.03 to 1 μmol/kg) i.v. mice | Analgesia | [79,80] | ||
Ro 64-6198 | NOP receptor nonpeptide agonist | 9.41 | 8.09 | 7.98 | (3 mg/kg) (1 mg/kg) intraperitoneal (i.p) mice (0.3 to 3 mg/kg) i.p. mice | Analgesia Additive analgesia anxiolytic-like effects | [81,82,83] |
(0.001–0.06 mg/kg), subcutaneous (s.c.) monkey | Analgesia No depression No itching No reinforcing | [17] | |||||
SCH221510 | Selective NOP receptor nonpeptide agonist | 0.3 | 12 | 1–30 mg/kg) peroral (p.o.) rat | anxiolytic-like effects | [84] | |
(0.1–3.0 mg/kg) i.p., p.o., intracolonic mice | potent anti-inflammatory and analgesic effect | [85] |
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El Daibani, A.; Che, T. Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain. Molecules 2022, 27, 595. https://doi.org/10.3390/molecules27030595
El Daibani A, Che T. Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain. Molecules. 2022; 27(3):595. https://doi.org/10.3390/molecules27030595
Chicago/Turabian StyleEl Daibani, Amal, and Tao Che. 2022. "Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain" Molecules 27, no. 3: 595. https://doi.org/10.3390/molecules27030595
APA StyleEl Daibani, A., & Che, T. (2022). Spotlight on Nociceptin/Orphanin FQ Receptor in the Treatment of Pain. Molecules, 27(3), 595. https://doi.org/10.3390/molecules27030595