A subtype-specific neuropeptide FF receptor antagonist attenuates morphine and nicotine withdrawal syndrome in the rat

Malin, David H.; Henceroth, Mallori M.; Elayoubi, Joanne; Campbell, Joseph R.; Anderson, Andrea P.; Goyarzu, Pilar; Izygon, Jonathan; Madison, Caitlin A.; Ward, Christopher P.; Burstein, Ethan S.

doi:10.1016/j.neulet.2018.06.053

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…There was only one study on the selective NPFFR1 antagonist, AC-262620, on nicotine dependence, and it was found that AC-262620 reduced the nicotinic antagonist mecamylamine precipitated withdrawal signs in nicotinedependent animals. 64 This result is consistent with the findings on opioid dependence and further suggests that NPFF antagonists may be the choice for treating drug dependence and withdrawal.…”

Section: Introductionsupporting

confidence: 90%

“…For example, the NPFF level was elevated in CSF from morphine-dependent rats but not nondependent rats . Activation of NPFFRs by NPFF or its analogues induced withdrawal-like signs or precipitated withdrawal syndrome − while blockade of NPFFRs with a nonselective antagonist dansyl-PQRamide, daY8Ra ( 13 , Table ), or selective NPFFR1 antagonist AC-262620 (structure not disclosed) prevented naloxone-precipitated morphine withdrawal syndrome. − Similarly, antagonism at both NPFFRs by antiserum or antisense reversed morphine tolerance and dependence in rats and mice , and blockade of NPFFRs with RF9 ( 14 , Table , Figure ) prevented the development of morphine tolerance and decreased naltrexone-precipitated withdrawal following chronic morphine treatment . Combined, these results consistently suggest that NPFFR antagonists or NPFFR1 selective antagonists have great potential for the treatment of opioid tolerance and dependence.…”

Section: Introductionmentioning

confidence: 91%

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Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development

Nguyễn

Marusich

et al. 2020

J. Med. Chem.

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The endogenous neuropeptide FF (NPFF) and its two cognate G protein-coupled receptors, Neuropeptide FF Receptors 1 and 2 (NPFFR1 and NPFFR2), represent a relatively new target system for many therapeutic applications including pain regulation, modulation of opioid side effects, drug reward, anxiety, cardiovascular conditions, and other peripheral effects. Since the cloning of NPFFR1 and NPFFR2 in 2000, significant progress has been made to understand their pharmacological roles and interactions with other receptor systems, notably the opioid receptors. A variety of NPFFR ligands with different mechanisms of action (agonists or antagonists) have been discovered although with limited subtype selectivities. Differential pharmacological effects have been observed for many of these NPFFR ligands, depending on assays/models employed and routes of administration. In this Perspective, we highlight the therapeutic potentials, current knowledge gaps, and latest updates of the development of peptidic and small molecule NPFFR ligands as tool compounds and therapeutic candidates.

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Section: Introductionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 91%

Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development

Nguyễn

Marusich

et al. 2020

J. Med. Chem.

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“…Prior research has demonstrated that NPFF exhibited antiopioid activity at the supraspinal level. ,,, Our results indicated that i.c.v. administration of NPFF receptor antagonist RF9 blocked the antiopioid activities of NPFF pharmacophore and endogenous NPFF systems and significantly potentiated the antinociception induced by sc administration of 1a and 1b , which supports the BBB permeability and NPFF agonistic activity observed in calcium mobilization assays.…”

Section: Discussionsupporting

confidence: 61%

All-Hydrocarbon Stapled Peptide Multifunctional Agonists at Opioid and Neuropeptide FF Receptors: Highly Potent, Long-Lasting Brain Permeant Analgesics with Diminished Side Effects

Zhang,

Xu,

et al. 2023

J. Med. Chem.

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“…Many reports have suggested multitarget drugs as promising candidates that can overcome the current limitations of single-target opioid analgesics . These drugs can simultaneously target opioid (μ-, κ-, δ-opioid or nociceptin/orphanin FQ peptide) and nonopioid [neuropeptide FF (NPFF), neurokinin-1, cholecystokinin, 5-hydroxytryptamine, neurotensin, and cannabinoid] receptors and exhibit multifunctional agonistic and/or antagonistic characteristics. − Among the nonopioid receptors, the NPFF system exhibited complex opioid-modulating effects, including pronociceptive (at the supraspinal level) and antinociceptive (at the spinal level) effects. − Previous reports have indicated that the NPFF system is implicated in opioid-induced side effects, including tolerance, hyperalgesia, abuse, anxiety, constipation, and respiratory depression. − Therefore, multifunctional opioid/NPFF receptor agonists are promising pharmacotherapeutic analgesics.…”

Section: Introductionmentioning

confidence: 99%

OFP011 Cyclic Peptide as a Multifunctional Agonist for Opioid/Neuropeptide FF Receptors with Improved Blood–Brain Barrier Penetration

Zhang

et al. 2022

ACS Chem. Neurosci.

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Mounting evidence indicates that the neuropeptide FF (NPFF) system is involved in the side effects of opioid usage, including antinociceptive tolerance, hyperalgesia, abuse, constipation, and respiratory depression. Our group recently discovered that the multitarget opioid/NPFF receptor agonist DN-9 exhibits peripheral antinociceptive activity. To improve its metabolic stability, antinociceptive potency, and duration, in this study, we designed and synthesized a novel cyclic disulfide analogue of DN-9, OFP011, and examined its bioactivity through in vitro cyclic adenosine monophosphate (cAMP) functional assays and in vivo behavioral experiments. OFP011 exhibited multifunctional agonistic effects at the μ-opioid and the NPFF 1 and NPFF 2 receptors and partial agonistic effects at the δand κ-opioid in vitro, as determined via the cAMP functional assays. Pharmacokinetic and pharmacological experiments revealed improvement in its blood− brain barrier permeability after systemic administration. In addition, subcutaneous OFP011 exhibited potent and long-lasting antinociceptive activity via the central μand κ-opioid receptors, as observed in different physiological and pathological pain models. At the highest antinociceptive doses, subcutaneous OFP011 exhibited limited tolerance, gastrointestinal transit, motor coordination, addiction, reward, and respiration depression. Notably, OFP011 exhibited potent oral antinociceptive activities in mouse models of acute, inflammatory, and neuropathic pain. These results suggest that the multifunctional opioid/NPFF receptor agonists with improved blood−brain barrier penetration are a promising strategy for long-term treatment of moderate to severe nociceptive and pathological pain with fewer side effects.

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A subtype-specific neuropeptide FF receptor antagonist attenuates morphine and nicotine withdrawal syndrome in the rat

Cited by 7 publications

References 39 publications

Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development

Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development

All-Hydrocarbon Stapled Peptide Multifunctional Agonists at Opioid and Neuropeptide FF Receptors: Highly Potent, Long-Lasting Brain Permeant Analgesics with Diminished Side Effects

OFP011 Cyclic Peptide as a Multifunctional Agonist for Opioid/Neuropeptide FF Receptors with Improved Blood–Brain Barrier Penetration

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