The NOP Receptor System in Neurological and Psychiatric Disorders: Discrepancies, Peculiarities and Clinical Progress in Developing Targeted Therapies

Toll, Lawrence; Cippitelli, Andrea; Ozawa, Akihiko

doi:10.1007/s40263-021-00821-0

Cited by 11 publications

(6 citation statements)

References 167 publications

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“…Unlike µ- and δ-opioid receptor subtypes, activation of ĸ-opioid and nociceptin opioid peptide (NOP) receptors are generally associated with a decrease in central monoaminergic activity (Gavioli and Calo, 2013; Schlicker and Morari, 2000; Tao and Auerbach, 2005; Yılmaz et al, 2006). It has also been suggested that agonists of ĸ- or NOP-receptors cause negative effects on mood (Ji et al, 2021; Toll et al, 2021), and blocking these receptors causes antidepressant-like effects (Jacobson et al, 2020; Park et al, 2019; Shang et al, 2021). Therefore, further studies are needed to clarify whether the antidepressant-like activity of tofisopam is associated with any attenuation in the functions of ĸ- and NOP-opioidergic receptors.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

et al. 2022

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Background: Depression is a disease that affects millions of people worldwide, and the discovery and development of effective and safe antidepressant drugs is one of the important topics of psychopharmacology. Objectives: In this study, it was aimed to investigate the antidepressant-like activity potential of tofisopam, an anxiolytic drug with 2,3-benzodiazepine structure, and to elucidate the pharmacological mechanisms mediating this effect. Methods: The antidepressant-like activity of tofisopam was investigated using tail suspension and modified forced swimming tests. Possible interactions of tofisopam with µ- and δ-opioid receptor subtypes were clarified by pharmacological antagonism, molecular docking and molecular dynamics simulation studies. Results: Tofisopam (50 and 100 mg/kg) significantly shortened the immobility time of mice in both the tail suspension and the modified forced swimming tests. The drug, at the same doses, prolonged the duration of swimming and climbing behaviours measured in modified forced swimming tests. A dosage of 25 mg/kg was ineffective. Mechanistic studies showed that the pretreatment with p-chlorophenylalanine methyl ester (serotonin synthesis inhibitor; 4 consecutive days, 100 mg/kg), α-methyl-para-tyrosine methyl ester (catecholamine synthesis inhibitor; 100 mg/kg), naloxonazine (selective µ-opioid receptor blocker, 7 mg/kg) and naltrindole (a selective δ-opioid receptor blocker, 0.99 mg/kg) abolished the anti-immobility effect induced by the 50 mg/kg dose of tofisopam in the tail suspension tests. Our in silico studies supported the behavioural findings that the antidepressant-like effect of tofisopam is mediated by μ- and δ-opioid receptors. Conclusion: This study is the first to show that tofisopam has antidepressant-like activity mediated by the serotonergic, catecholaminergic and opioidergic systems.

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Section: Discussionmentioning

confidence: 99%

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

et al. 2022

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“…Nociceptin was first isolated and found to induce a decrease of latencies in hot plate and tail flick tests after intracerebroventricular injection in mice [41]. Later, it was discovered that nociceptin mediated the blocking of opioid-receptors-induced analgesia [42]. The nociceptins family have a Phe residue in the N-terminus, compared with the N-terminal Tyr in the other families of endogenous peptides (Figure 2), and participate in numerous biological activities, such as substance abuse, analgesia control, memory, posttraumatic stress disorder, neuronal differentiation, and cell proliferation [43][44][45].…”

Section: Nociceptinsmentioning

confidence: 99%

“…Nociceptin, a heptadecapeptide, binds and activates NOP, exhibiting a unique functional profile that relates to and distinguishes the receptor system from the considered classical opioid receptors (MOP, DOP, and KOP) [42,81,82]. Unlike the endogenous opioid peptides, a Phe residue, instead of Tyr, appears at its N-terminal end (Figure 2).…”

Section: The Nociceptin/orphanin Fq Receptor (Nop)mentioning

confidence: 99%

“…Hence, its modulatory role in numerous biological activities, from analgesia to intermediary metabolism or cell growth control. Recent research focuses on OR distribution and capacities related to their function and dysfunction in different pathologies, including cancer (see, for example, [42,[94][95][96][97][98][99]). The structure of ZOP is different from the structure of OR.…”

Section: The Distribution Of Ormentioning

confidence: 99%

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Involvement of the Opioid Peptide Family in Cancer Progression

2023

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Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins) in cancer development. Anticancer therapeutic strategies targeting the opioid peptidergic system and the main research lines to be developed regarding the topic reviewed are suggested. There is much to investigate about opioid peptides and cancer: basic information is scarce, incomplete, or absent in many tumors. This knowledge is crucial since promising anticancer strategies could be developed alone or in combination therapies with chemotherapy/radiotherapy.

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“…A major achievement was the identification of the nociceptin opioid peptide receptor (NOR), which in humans is encoded via the opioid receptor-like-1 (ORL-1) gene. It is a G protein-coupled receptor with homology to classical opioid receptors but it lacks the ability to bind opioid ligands [12]. NOR shares partial homology to MOR, KOR and DOR, and it is insensitive to opioid agonists, such as morphine.…”

Section: Introductionmentioning

confidence: 99%

Naturally Inspired Molecules for Neuropathic Pain Inhibition—Effect of Mirogabalin and Cebranopadol on Mechanical and Thermal Nociceptive Threshold in Mice

Sałat,

Zaręba,

Awtoniuk

et al. 2023

Molecules

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Background: Neuropathic pain is drug-resistant to available analgesics and therefore novel treatment options for this debilitating clinical condition are urgently needed. Recently, two drug candidates, namely mirogabalin and cebranopadol have become a subject of interest because of their potential utility as analgesics for chronic pain treatment. However, they have not been investigated thoroughly in some types of neuropathic pain, both in humans and experimental animals. Methods: This study used the von Frey test, the hot plate test and the two-plate thermal place preference test supported by image analysis and machine learning to assess the effect of intraperitoneal mirogabalin and subcutaneous cebranopadol on mechanical and thermal nociceptive threshold in mouse models of neuropathic pain induced by streptozotocin, paclitaxel and oxaliplatin. Results: Mirogabalin and cebranopadol effectively attenuated tactile allodynia in models of neuropathic pain induced by streptozotocin and paclitaxel. Cebranopadol was more effective than mirogabalin in this respect. Both drugs also elevated the heat nociceptive threshold in mice. In the oxaliplatin model, cebranopadol and mirogabalin reduced cold-exacerbated pain. Conclusions: Since mirogabalin and cebranopadol are effective in animal models of neuropathic pain, they seem to be promising novel therapies for various types of neuropathic pain in patients, in particular those who are resistant to available analgesics.

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The NOP Receptor System in Neurological and Psychiatric Disorders: Discrepancies, Peculiarities and Clinical Progress in Developing Targeted Therapies

Cited by 11 publications

References 167 publications

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study

Involvement of the Opioid Peptide Family in Cancer Progression

Naturally Inspired Molecules for Neuropathic Pain Inhibition—Effect of Mirogabalin and Cebranopadol on Mechanical and Thermal Nociceptive Threshold in Mice

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