Dissociation of pharmacological pro- and anti-opioid effects by neuropeptide FF analogs

Quelven, Isabelle; Roussin, Anne; Burlet‐Schiltz, Odile; Gouardères, Christine; Tafani, Jean-André Mathieu; Mazarguil, Honoré; Zajac, Jean‐Marie

doi:10.1016/s0014-2999(02)01983-0

Cited by 29 publications

(14 citation statements)

References 28 publications

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“…Neuropeptide FF (NPFF) is an endogenous opioid-modulating peptide and plays opioid-modulating roles in antinociception, tolerance, and addition. − In our previous studies, several multifunctional peptides with opioid/neuropeptide FF receptor agonistic activities, such as EN-9, BN-9 (analog 0 ), and DN-9, were characterized that could produce nontolerant antinociception. − Our data showed that 0 simultaneously activated opioid and NPFF receptors and produced potent nontolerance-forming antinociception for 1.5 h after central or peripheral injection. , However, recent pharmacological characterization has shown that 0 could not cross the blood–brain barrier (BBB) . In carrageenan-induced hindpaw inflammation model, the antiallodynic potency of BN-9 after central administration was more potent than that of BN-9 given systemically .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Characterization of Cyclic Disulfide-Containing Peptide Analogs of the Multifunctional Opioid/Neuropeptide FF Receptor Agonists That Produce Long-Lasting and Nontolerant Antinociception

Zhang

et al. 2020

J. Med. Chem.

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In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist 0 (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized. The cyclized analogs and their linear counterparts behaved as multifunctional agonists at both opioid and NPFF receptors in vitro and produced potent analgesia without tolerance development. In comparison to 0, cyclized peptide 6 exhibited sevenfold more potent μ-opioid receptor agonistic activity in vitro. Interestingly, the cyclized analog 6 possessed an improved stability in the brain and an increased blood–brain barrier permeability compared to the parent peptide 0 and produced more potent analgesia after supraspinal or subcutaneous administration with improved duration of action of 4 h. In addition, antinociceptive tolerance of analog 6 was greatly reduced after subcutaneous injection compared to fentanyl, as was the rewarding effect, withdrawal reaction, and gastrointestinal inhibition.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Characterization of Cyclic Disulfide-Containing Peptide Analogs of the Multifunctional Opioid/Neuropeptide FF Receptor Agonists That Produce Long-Lasting and Nontolerant Antinociception

Zhang

et al. 2020

J. Med. Chem.

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“…[21,22]). In mice, the intrathecal injection of 1DMe also potentiates morphine analgesia [64]. Both the antinociception and the potentiation of the morphine-induced analgesia elicited by NPFF analogs are blocked by delta and mu opioid antagonists, suggesting the involvement of these opioid receptor types in mediating the NPFF effects [65][66][67].…”

Section: Painmentioning

confidence: 95%

Opioid-modulating Peptides: Mechanisms of Action

Mollereau¹,

Roumy²,

Zajac

2005

CTMC

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Opioids are involved in the physiological control of numerous functions of the central nervous system, particularly nociception. It appears that some endogenous neuropeptides, called anti-opioids, participate in an homeostatic system tending to reduce the effects of opioids. Neuropeptide FF (NPFF) and cholecystokinin (CCK) possess these properties and, paradoxically, the opioid peptides nociceptin and dynorphin display some anti-opioid activity. All these peptides exhibit complex properties as they are able to both counteract and potentiate opioid activity, acting rather as modulators of opioid functions. The purpose of this review is to highlight that two different mechanisms are clearly involved in the control of opioid functions by opioid-modulating peptides: a circuitry-induced mechanism for nociceptin and dynorphin, and a cellular anti-opioid mechanism for NPFF and CCK. The knowledge of these mechanisms has potential therapeutic interest in the control of opioid functions, notably for alleviating pain and/or for the treatment of opioid abuse.

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“…However, it should be noted that other studies have reported a loss of pro‐opioid activity of NPFF after carrageenan inflammation [29] and a lack of sensitivity to naloxone of the anti‐allodynic effect of 1DMe in neuropathic rats [30]. In mice, the intrathecal injection of 1DMe also potentiates morphine analgesia [31]. Both the antinociception and the potentiation of morphine‐induced analgesia elicited by NPFF analogs are blocked by delta and mu opioid antagonists, suggesting the involvement of these two opioid receptor types in mediating indirectly NPFF effects [32–34].…”

Section: Pharmacological Cross‐talkmentioning

confidence: 99%

“…From a therapeutic point of view, it would be important to study the effect of NPFF agonists after systemic injection. Intraperitoneal injection of 1DMe has been shown to induce anti‐opioid activity at low dose and pro‐opioid activity at higher dose in the mouse tail flick test [31], while systemic dNPA was anti‐opioid in the same test [41]. Further progress will depend on the development of small molecules showing high specificity towards receptor subtypes and a better capacity to cross the blood brain barrier.…”

Section: Pharmacological Cross‐talkmentioning

confidence: 99%

Opioid‐modulating properties of the neuropeptide FF system

2010

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Opioid receptors are involved in the control of pain perception in the central nervous system together with endogenous neuropeptides, termed opioid-modulating peptides, participating in a homeostatic system. Neuropeptide FF (NPFF) and related peptides possess anti-opioid properties, the cellular mechanisms of which are still unclear. The purpose of this review is to detail the phenomenon of cross-talk taking place between opioid and NPFF systems at the in vivo pharmacological level and to propose cellular and molecular models of functioning. A better knowledge of the mechanisms underlying opioid-modulating properties of NPFF has potential therapeutic interest for the control of opioid functions, notably for alleviating pain and/or for the treatment of opioid abuse.

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Dissociation of pharmacological pro- and anti-opioid effects by neuropeptide FF analogs

Cited by 29 publications

References 28 publications

Synthesis and Biological Characterization of Cyclic Disulfide-Containing Peptide Analogs of the Multifunctional Opioid/Neuropeptide FF Receptor Agonists That Produce Long-Lasting and Nontolerant Antinociception

Synthesis and Biological Characterization of Cyclic Disulfide-Containing Peptide Analogs of the Multifunctional Opioid/Neuropeptide FF Receptor Agonists That Produce Long-Lasting and Nontolerant Antinociception

Opioid-modulating Peptides: Mechanisms of Action

Opioid‐modulating properties of the neuropeptide FF system

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